Oligosaccharide Compounds

ABSTRACT

The invention relates generally to oligosaccharide compounds and the use of these compounds as pharmaceuticals for treating diseases or conditions in which it is desirable to inhibit β-secretase.

TECHNICAL FIELD

This invention relates generally to oligosaccharide compounds, the useof these compounds as pharmaceuticals, pharmaceutical compositionscontaining the compounds, processes for preparing the compounds, andmethods of treating diseases or conditions in which it is desirable toinhibit β-secretase.

BACKGROUND

As populations age neurodegenerative disorders such as Alzheimer'sdisease become more prevalent. Alzheimer's disease is a common form ofdementia, and is progressive and irreversible. The pathogenesis of thedisease is thought to involve cerebral deposits of aggregated amyloidβ-peptide. The first (and rate-limiting) step in the generation ofamyloid β-peptide is cleavage of amyloid precursor protein byβ-secretase (β-site amyloid precursor protein cleaving enzyme-1,β-secretase-1, hereinafter “BACE-1”). This makes BACE-1 an attractivetarget for new Alzheimer's therapies.

Heparan sulfate (HS) and its highly sulfated analogue heparin have beenshown to inhibit BACE-1 activity. HS and heparin are bothglycosaminoglycans comprising 1,4-linked disaccharide units ofβ-D-iduronic acid or α-L-iduronic acid with N-acetyl-α-D-glucosamine(dominant in the case of HS) or N-sulfo-α-D-glucosamine (dominant in thecase of heparin) and additional O-sulfate ester substituents. Heparin isa well-known pharmaceutical with anti-coagulant activity. However, theanti-coagulant properties of heparin need to be attenuated if it is tobe used for other pharmaceutical applications otherwise possible sideeffects, such as internal bleeding and impaired blood clotting, can beproblematic.

Turnbull et al. have examined the activities of modified heparinsagainst BACE-1 (S. J. Patey, E. A. Edwards, E. A. Yates, J. E. Turnbull,J. Med. Chem. 2006, 49, 6129-6132). They found that, after porcinemucosal heparin (PIMH), the next most effective inhibitor was a modifiedPIMH which had undergone N-desulfation and N-re-acetylation. Turnbull etal. also reported the preparation of oligosaccharides by enzymaticdigestion of PIMH, and the activities of these oligosaccharides againstBACE-1 were also determined. They found that the decasaccharide fractionwas about 40-fold less active than PIMH, and the octasaccharide fractionwas 10-fold less active than the decasaccharide fraction.Oligosaccharides containing 18 saccharide units were about as active asPIMH itself. As these oligosaccharide fractions are derived from a verycomplex polymer, the derived fractions are not single chemical species.

WO 2007/138263 describes a study by Scholefield et al. that showed thatan N-acetylated heparin which is highly sulfated at the 2-O and 6-Opositions is active against BACE-1 and that removal of the 2-O or 6-Osulfates decreased the activity against BACE-1. WO 2007/138263 suggeststhat removal of one or more sulfates would therefore be expected to havea deleterious effect on the activity. WO 2007/138263 describes andclaims such de-sulfated oligosaccharides. WO 2007/138263 further statesthat neither N- nor 2-O-sulfation is an absolute requirement for highlevel activity when accompanied by 6-O sulfation. As theseoligosaccharide fractions are derived from a very complex polymer, thederived fractions are not single chemical species.

WO 2010/029185 describes oligosaccharides, including decasaccharides andoctasaccharides, which are said to be heparan sulfate mimetics anduseful in the treatment of cancer, pathological angiogenesis and/or forinducing hematopoietic stem cell mobilisation. These oligosaccharideshave an L-iduronic acid moiety at the non-reducing terminus.

There is a need for further oligosaccharides which are inhibitors ofBACE-1. Furthermore, if such oligosaccharides were synthetic, in otherwords, if they could be synthesised de novo, they would, advantageously,be well-characterised single chemical entities. This would make themattractive for use as pharmaceuticals.

It is therefore an object of the present invention to provideoligosaccharide compounds that are inhibitors of BACE-1, or to at leastprovide a useful choice.

SUMMARY OF INVENTION

In a first aspect, the present invention provides an octasaccharide,decasaccharide or dodecasaccharide compound of the formula (I):

H-Q-V-W-X-Y-Z-A   (I)

where:

A is an optionally substituted alkoxy, aralkoxy, aryloxy group;

W, X, Y and Z are each independently a disaccharide of formula (i);

V is a disaccharide of formula (i) or V is absent; and

Q is a disaccharide of formula (i) or Q is absent

where:

R¹ is SO₃H;

R² is H;

R³ is acyl;

R⁴ is H or SO₃H; and

each R⁵ and R⁶ is independently selected from COOH and H; provided thatone of R⁵ and R⁶ in each disaccharide is H and the other is COOH;

and provided that all R³ groups in the octasaccharide, decasaccharide ordodecasaccharide are the same as each other and provided that all R⁴groups in the octasaccharide, decasaccharide or dodecasaccharide are thesame as each other; or a pharmaceutically acceptable salt thereof.

Preferably R⁵ is H and R⁶ is COOH. Alternatively it is preferred that R⁵is COOH and R⁶ is H. Alternatively, the octasaccharide, decasaccharideor dodecasaccharide contains at least one disaccharide of formula (i)where R⁵ is H and R⁶ is COOH and at least one disaccharide of formula(i) where R⁵ is COOH and R⁶ is H.

In a second aspect, the present invention provides an octasaccharide,decasaccharide or dodecasaccharide compound of the formula (Ia):

H-Q-V-W-X-Y-Z-A   (Ia)

where:

A is an optionally substituted alkoxy, aralkoxy, aryloxy group;

W, X, Y and Z are each independently a disaccharide of formula (i);

V is a disaccharide of formula (i) or V is absent; and

Q is a disaccharide of formula (i) or Q is absent

where:

R¹ is SO₃H;

R² is H;

R³ is acyl;

R⁴ is H or SO₃H;

R⁵ is H; and

R⁶ is COOH;

provided that all R³ groups in the octasaccharide, decasaccharide ordodecasaccharide are the same as each other and provided that all R⁴groups in the octasaccharide, decasaccharide or dodecasaccharide are thesame as each other; or a pharmaceutically acceptable salt thereof.

In a third aspect, the present invention provides an octasaccharide,decasaccharide or dodecasaccharide compound of the formula (Ib):

H-Q-V-W-X-Y-Z-A   (Ib)

where:

A is an optionally substituted alkoxy, aralkoxy, aryloxy group;

W, X, Y and Z are each independently a disaccharide of formula (i);

V is a disaccharide of formula (i) or V is absent; and

Q is a disaccharide of formula (i) or Q is absent

where:

R¹ is SO₃H;

R² is H;

R³ is acyl;

R⁴ is H or SO₃H;

R⁵ is COOH; and

R⁶ is H;

provided that all R³ groups in the octasaccharide, decasaccharide ordodecasaccharide are the same as each other and provided that all R⁴groups in the octasaccharide, decasaccharide or dodecasaccharide are thesame as each other; or a pharmaceutically acceptable salt thereof.

Preferably the pharmaceutically acceptable salt is an ammonium salt, ametal salt, e.g. a sodium salt, or a salt of an organic cation, or amixture thereof.

In some examples, Q and V are absent and the compound of formula (I),(Ia) or (Ib) is an octasaccharide.

In other examples, one of Q or V is absent and the other is adisaccharide of formula (i) and the compound of formula (I), (Ia) or(Ib) is a decasaccharide.

In still other examples, Q and V are each independently a disaccharideof formula (i) and the compound of formula (I), (Ia) or (Ib) is adodecasaccharide.

Preferably R³ is a lower acyl group, e.g. an acetyl group.

Preferably R⁴ is SO₃H or a salt form thereof, e.g. R⁴ may be SO₃Na orSO₃NH₄. Alternatively it is preferred that R⁴ is H.

In some examples R¹ is a salt form of SO₃H, e.g. R¹ may be SO₃NH₄ orSO₃Na.

In some examples R⁵ or R⁶ is a salt form of COOH, e.g. R⁵ or R⁶ may beCOONa or COONH₄.

Preferably A is an optionally substituted aryloxy group, such as anaryloxy group, e.g. a phenoxy group, substituted with an alkoxy group,e.g. a lower alkoxy group, e.g. a 4-methoxyphenoxy group.

Alternatively A is an optionally substituted alkoxy group, preferablyhexyloxy or octyloxy group, or an ω-(N-benzyloxycarbonylamino)-alkyloxygroup, preferably an 8-(N-benzyloxycarbonylamino)-octyl, or6-(N-benzyloxycarbonylamino)hexyl group, or an ω-aminoalkyloxy group,preferably an 8-aminooctyl or 6-aminohexyl group, or amethoxy-per(ethyleneoxy) group, preferably amethoxy-tris(ethylenoxy)-group.

In another aspect the invention provides a compound selected from thegroup consisting of:

or a pharmaceutically acceptable salt thereof.

In another aspect the invention provides a compound selected from thegroup consisting of:

or a pharmaceutically acceptable salt thereof.

The invention also provides an acid form of any one of the compounds (a)to (g) or (j) to (p) above.

In another aspect, the invention provides a prodrug, e.g. an esterprodrug, of a compound of formula (I), (Ia) or (Ib).

In another aspect the invention provides a compound of formula 13, 14,15, 16 or 27:

In another aspect the invention provides a crystalline compound offormula 13, 14, 15, 16 or 27:

In another aspect, the invention provides a crystalline compound offormula 13, having a melting point of about 131° C.

In another aspect, the invention provides a crystalline compound offormula 14, having a melting point of about 140-141° C.

In another aspect, the invention provides a crystalline compound offormula 16, having a melting point of about 144° C.

In another aspect, the invention provides a crystalline compound offormula 27, having a melting point of about 144° C.

In another aspect, the invention provides a crystalline compound offormula 13, having:

-   -   i. a crystal structure as shown in FIG. 1; and/or    -   ii. crystal lattice parameters at 123(2) K of: a=10.454(2) Å,        b=35.610(7) Å, c=14.408(3) Å, α=90°, β=95.61(3)°, γ=90°; and/or    -   iii. a crystal structure belonging to a monoclinic space group,        e.g. P2₁

determined by X-ray crystal structure analysis

In another aspect, the invention provides a crystalline compound offormula 14, having:

-   -   i. a crystal structure as shown in FIG. 2; and/or    -   ii. crystal lattice parameters at 164(2) K of: a=9.2713(7) Å,        b=17.4067(11) Å, c=15.0036(11) Å, a=90°, β=97.449(7)°, γ=90°;        and/or    -   iii. a crystal structure belonging to a monoclinic space group,        e.g. P2₁

determined by X-ray crystal structure analysis

In another aspect, the invention provides a crystalline compound offormula 15, having:

-   -   i. a crystal structure as shown in FIG. 3; and/or    -   ii. crystal lattice parameters at 118(2) K of: a=38.3346(13) Å,        b=8.0744(3) Å, c=16.1659(6) Å, α=90°, β=91.222(2)°, γ=90°;        and/or    -   iii. a crystal structure belonging to a monoclinic space group,        e.g. C2

determined by X-ray crystal structure analysis

In another aspect, the invention provides a crystalline compound offormula 16, having:

-   -   i. a crystal structure as shown in FIG. 4; and/or    -   ii. crystal lattice parameters at 123(2) K of: a=14.8343(11) Å,        b=8.4771(6) Å, c=21.8112(17) Å, α=90°, β=91.780(7)°, γ=90°;        and/or    -   iii. a crystal structure belonging to a monoclinic space group,        e.g. P2₁

determined by X-ray crystal structure analysis

In another aspect, the invention provides a crystalline compound offormula 27, having:

-   -   i. a crystal structure as shown in FIG. 5; and/or    -   ii. crystal lattice parameters at 164(2) K of: a=8.1104(2) Å,        b=19.5548(6) Å, c=27.2321(19) Å, α=90°, β=90°, γ=90°; and/or    -   iii. a crystal structure belonging to a orthorhombic space        group, e.g. P2₁2₁2₁

determined by X-ray crystal structure analysis

In another aspect the invention provides the use of a compound offormula 13, 14, 15, 16 or 27 for preparing a compound of formula (I),(Ia) or (Ib).

In another aspect the invention provides a composition comprising apharmaceutically effective amount of a compound of formula (I), (Ia) or(Ib) and optionally a carrier.

In another aspect the invention provides a pharmaceutical compositioncomprising a pharmaceutically effective amount of a compound of formula(I), (Ia) or (Ib) and optionally a pharmaceutically acceptable carrier,diluent or excipient.

In another aspect the invention provides a compound of formula (I), (Ia)or (Ib) in combination with at least one other compound, e.g. a seconddrug compound. The other compound may be, for example, anoligosaccharide compound, a cyclitol such as scyllo-inositol orD-chiro-inositol, an acetylcholinesterase inhibitor, a nicotinicagonist, an antibody targeting β-amyloid, an inhibitor of β-amyloid, aninhibitor of tau aggregation or memantine.

In another aspect the invention provides the use of a compound offormula (I), (Ia) or (Ib) for inhibiting BACE-1.

In another aspect the invention provides the use of a compound offormula (I), (Ia) or (Ib) as a medicament.

In another aspect the invention provides the use of a compound offormula (I), (Ia) or (Ib) for treating or preventing a disease ordisorder in which it is desirable to inhibit BACE-1.

In another aspect the invention provides the use of a compound offormula (I), (Ia) or (Ib) for treating or preventing a neurodegenerativedisorder such as senile dementia, pre-senile dementia, multi-infarctdementia or Alzheimer's disease, preferably Alzheimer's disease.

In another aspect the invention provides the use of a pharmaceuticalcomposition comprising a pharmaceutically effective amount of a compoundof formula (I), (Ia) or (Ib) for treating or preventing a disease ordisorder in which it is desirable to inhibit BACE-1.

In another aspect the invention provides the use of a pharmaceuticalcomposition comprising a pharmaceutically effective amount of a compoundof formula (I), (Ia) or (Ib) for treating or preventing aneurodegenerative disorder such as senile dementia, pre-senile dementia,multi-infarct dementia or Alzheimer's disease, preferably Alzheimer'sdisease.

In another aspect the invention provides the use of a compound offormula (I), (Ia) or (Ib) for use in the manufacture of a medicament.

In another aspect the invention provides a pharmaceutical compositionfor treating or preventing a disease or disorder in which it isdesirable to inhibit BACE-1 comprising a compound of formula (I), (Ia)or (Ib).

In another aspect the invention provides a pharmaceutical compositionfor treating or preventing a neurodegenerative disorder such as seniledementia, pre-senile dementia, multi-infarct dementia or Alzheimer'sdisease, preferably Alzheimer's disease, comprising a compound offormula (I), (Ia) or (Ib).

In another aspect the invention provides the use of a compound offormula (I), (Ia) or (Ib) in the manufacture of a medicament for thetreatment or prevention of a disease or disorder in which it isdesirable to inhibit BACE-1.

In another aspect the invention provides a method of treating orpreventing a disease or disorder in which it is desirable to inhibitBACE-1 comprising administering a pharmaceutically effective amount of acompound of formula (I), (Ia) or (Ib) to a patient requiring treatment.

In another aspect the invention provides a method of treating orpreventing a neurodegenerative disorder such as senile dementia,pre-senile dementia, multi-infarct dementia or Alzheimer's disease,preferably Alzheimer's disease, comprising administering apharmaceutically effective amount of a compound of formula (I), (Ia) or(Ib) to a patient requiring treatment.

In another aspect the invention provides the use of a compound offormula (I), (Ia) or (Ib) in combination with at least one othercompound, e.g. a second drug compound, e.g. an oligosaccharide compound,a cyclitol such as scyllo-inositol or D-chiro-inositol, anacetylcholinesterase inhibitor, a nicotinic agonist, an antibodytargeting β-amyloid, an inhibitor of β-amyloid, an inhibitor of tauaggregation or memantine, for treating or preventing a disease ordisorder in which it is desirable to inhibit BACE-1 (e.g. aneurodegenerative disorder such as senile dementia, pre-senile dementia,multi-infarct dementia or Alzheimer's disease, preferably Alzheimer'sdisease).

In another aspect the invention provides a method of treating orpreventing a disease or disorder in which it is desirable to inhibitBACE-1 (e.g. a neurodegenerative disorder such as senile dementia,pre-senile dementia, multi-infarct dementia or Alzheimer's disease,preferably Alzheimer's disease) comprising administering apharmaceutically effective amount of a compound of formula (I), (Ia) or(Ib) in combination with at least one other compound, e.g. a second drugcompound, e.g. an oligosaccharide compound, a cyclitol such asscyllo-inositol or D-chiro-inositol, an acetylcholinesterase inhibitor,a nicotinic agonist, an antibody targeting β-amyloid, an inhibitor ofβ-amyloid, an inhibitor of tau aggregation or memantine. The compound offormula (I), (Ia) or (Ib) and the other compound may be administeredseparately, simultaneously or sequentially.

The diseases or disorders include neurodegenerative disorders such assenile dementia, pre-senile dementia, multi-infarct dementia orAlzheimer's disease, preferably Alzheimer's disease. 15

The compound of formula (I), (Ia) or (Ib) may be selected from the groupconsisting of compounds (a) to (g) and (j) to (p) as defined above.

Compounds of formulae (I), (Ia) or (Ib) are hereinafter described as“compounds of the invention”. A compound of the invention includes acompound in any form, e.g. in free form or in the form of a salt or asolvate. For example, the compounds of the invention, e.g. the compoundsof formula (I), (Ia), (Ib) and the compounds (a) to (g) and (j) to (p)can exist as the free acid form and the invention is intended to coversuch acid forms.

It will be appreciated that any of the sub-scopes disclosed herein, e.g.with respect to R¹, R², R³, R⁴, R⁵, R⁶, A, Q, V, W, X, Y and Z may becombined with any of the other sub-scopes disclosed herein to producefurther sub-scopes.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows an ORTEP diagram of compound 13.

FIG. 2 shows an ORTEP diagram of compound 14.

FIG. 3 shows an ORTEP diagram of compound 15.

FIG. 4 shows an ORTEP diagram of compound 16.

FIG. 5 shows an ORTEP diagram of compound 27.

DETAILED DESCRIPTION

Definitions

The term “alkyl” means any saturated hydrocarbon radical having up to 30carbon atoms and includes any C₁-C₂₅, C₁-C₂₀, C₁-C₁₅, C₁-C₁₀, or C₁-C₆alkyl group, and is intended to include cyclic, straight- andbranched-chain alkyl groups. Cyclic alkyl groups include those groupshaving one or more ring oxygen atoms. Examples of alkyl groups include:methyl group, ethyl group, n-propyl group, iso-propyl group, n-butylgroup, iso-butyl group, sec-butyl group, t-butyl group, n-pentyl group,1,1-dimethylpropyl group, 1,2-dimethylpropyl group, 2,2-dimethylpropylgroup, 1-ethylpropyl group, 2-ethylpropyl group, n-hexyl group,1,2-dimethylbutyl group, cyclopropyl group, cyclobutyl group,cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctylgroup, tetrahydrofuranyl group and tetrahydropyranyl group.

The term “lower alkyl” means any saturated hydrocarbon radical havingfrom 1 to 6 carbon atoms and is intended to include cyclic, straight-and branched-chain alkyl groups.

The term “alkoxy” means —OR where R is alkyl as defined above. The term“lower alkoxy” means —OR where R is lower alkyl as defined above.

Any alkoxy group may optionally be substituted with one or moresubstituents selected from the group consisting of fluorine, chlorine,methoxy, ethoxy,

O(CH₂CH₂)_(n)OMe where n is 1-10, NH₂, NHCO₂Bn, and CO₂H orpharmaceutically acceptable salt form thereof.

The term “aryl” means an aromatic radical having 4 to 18 carbon atomsand includes heteroaromatic radicals. Examples include monocyclicgroups, as well as fused groups such as bicyclic groups and tricyclicgroups. Some examples include phenyl group, indenyl group, 1-naphthylgroup, 2-naphthyl group, azulenyl group, heptalenyl group, biphenylgroup, indacenyl group, acenaphthyl group, fluorenyl group, phenalenylgroup, phenanthrenyl group, anthracenyl group, cyclopentacyclooctenylgroup, and benzocyclooctenyl group, pyridyl group, pyrrolyl group,pyridazinyl group, pyrimidinyl group, pyrazinyl group, triazolyl group(including a 1-H-1,2,3-triazol-1-yl and a 1-H-1,2,3-triazol-4-yl group),tetrazolyl group, benzotriazolyl group, pyrazolyl group, imidazolylgroup, benzimidazolyl group, indolyl group, isoindolyl group,indolizinyl group, purinyl group, indazolyl group, furyl group, pyranylgroup, benzofuryl group, isobenzofuryl group, thienyl group, thiazolylgroup, isothiazolyl group, benzothiazolyl group, oxazolyl group, andisoxazolyl group.

Any aryl group may optionally be substituted with one or moresubstituents selected from the group consisting of fluorine, chlorine,alkoxy (including methoxy and ethyoxy), alkyl (including methyl andethyl), cyano, acylamino, azido or NHCO₂Bn.

The term “aryloxy” means —OR′ where R′ is aryl as defined above.

The term “aralkyl” means an aryl group covalently linked to an alkylenegroup.

The term “aralkoxy” means —OR″ where R″ is aralkyl as defined above.

Any aralkoxy group may optionally be substituted with one or moresubstituents selected from the group consisting of fluorine, chlorine,alkoxy (including methoxy and ethyoxy), alkyl (including methyl andethyl), cyano, acylamino, azido or NHCO₂Bn.

The term “acyl” means

where R′″ is alkyl, aralkyl or aryl as defined above. The term “loweracyl” means a C₂-C₆ acyl group, having a corresponding meaning to “loweralkyl” as defined above.

The term “halogen” includes fluorine, chlorine, bromine and iodine.

The term “prodrug” as used herein means a pharmacologically acceptablederivative of the compounds of formulae (I), (Ia) and (Ib), such that anin vivo biotransformation of the derivative gives the compound asdefined in formulae (I), (Ia) and (Ib). Prodrugs of compounds offormulae (I), (Ia) and (Ib) may be prepared by modifying functionalgroups present in the compounds in such a way that the modifications arecleaved in vivo to give the parent compound. Typically, prodrugs of thecompounds of formulae (I), (Ia) and (Ib) will be ester prodrug forms.

The term “pharmaceutically acceptable salts” is intended to apply tonon-toxic salts such as ammonium salts, metal salts, e.g. sodium salts,or salts of organic cations, or a mixture thereof.

The term “protecting group” means a group that selectively protects anorganic functional group, temporarily masking the chemistry of thatfunctional group and allowing other sites in the molecule to bemanipulated without affecting the functional group. Suitable protectinggroups are known to those skilled in the art and are described, forexample, in Protective Groups in Organic Synthesis (3^(rd) Ed.), T. W.Greene and P. G. M. Wuts, John Wiley & Sons Inc (1999). Examples ofprotecting groups include, but are not limited to: O-benzyl,O-benzhydryl, O-trityl, O-tert-butyldimethylsilyl,O-tert-butyldiphenylsilyl, O-4-methylbenzyl, O-acetyl, O-chloroacetyl,O-methoxyacetyl, O-benzoyl, O-4-bromobenzoyl, O-4-methylbenzoyl,O-fluorenylmethoxycarbonyl and O-levulinoyl.

The term “patient” includes human and non-human animals.

The terms “treatment”, “treating” and the like include the alleviationof one or more symptoms, or improvement of a state associated with thedisease or disorder, for example, improvement in cognition, improvementin memory function.

The terms “preventing”, “prevention” and the like include the preventionof one or more symptoms associated with the disease or disorder.

The Compounds of the Invention

The compounds of the invention, particularly those exemplified, areinhibitors of BACE-1 and are useful as pharmaceuticals, particularly forthe treatment or prevention of diseases or conditions in which it isdesirable to inhibit BACE-1, e.g. neurodegenerative disorders such assenile dementia, pre-senile dementia, multi-infarct dementia orAlzheimer's disease, particularly Alzheimer's disease. The compounds ofthe invention are useful in both free base form and in the form of saltsand/or solvates.

Those skilled in the art will appreciate that the compounds of theinvention can exist as stereoisomers. For example, depending on thestereochemistry at the carbon marked (#) in the disaccharide of formula(i), the disaccharide can be either gluco or ido form. Thus, each R⁵ andeach R⁶ in each disaccharide of formula (i) is independently selectedfrom COOH and H; provided that one of R⁵ and R⁶ in each disaccharide isH and the other is COOH.

The octasaccharides, decasaccharides and dodecasaccharides of theinvention are made up of the disaccharides of formula (i). The skilledperson will therefore further appreciate that the octasaccharides,decasaccharides and dodecasaccharides of the invention may be all glucoform (where all disaccharides of formula (i) in the compound are gluco),all ido form (where all disaccharides of formula (i) in the compound areido) or a mixture of gluco and ido forms (where the disaccharides offormula (i) in the compound are a mixture of gluco and ido).

As described in Example 4, heparin has an IC₅₀ of 0.002 μg/mL againsthuman recombinant BACE-1 and N-acetylated low molecular weight heparin(NAcLMWH) has an IC₅₀ of 0.007 μg/mL. Surprisingly, the oligosaccharidesof the invention are potent inhibitors of BACE-1. For example, compounds90, 91 and 92 all have an IC₅₀ of about 0.01 μg/mL against humanrecombinant BACE-1. Indeed, some compounds of the invention are onlyapproximately 5-fold less potent than heparin by mass. This issurprising when compared to the activities of the octasaccharide anddecasaccharide fractions reported in J. Med. Chem. 2006, 49, 6129-6132,and indicates a role for synthetic oligosaccharides in treating diseasesor disorders where it is desirable to inhibit BACE-1. The syntheticoligosaccharides of the invention also have the advantage that they arediscrete chemical entities of known structure.

Interestingly, not only are the 6-sulfated compounds of the inventionsurprisingly potent synthetic oligosaccharides, but, even moresurprisingly, the synthetic oligosaccharides of the invention which aresulfated at the 2- and 6-positions tend to be significantly more activethan the corresponding 6-sulfated oligosaccharides. This would not havebeen predicted based on previous studies on modified full lengthheparins.

Advantageously, the compounds of the invention have attentuatedanti-coagulent activity. Referring to Example 5, none of the compoundsof the invention display any measurable ability to accelerateantithrombin-III mediated inactivation of Factor Xa, as measured bycleavage of a peptide substrate.

The compounds of the invention may be administered to a patient by avariety of routes, including orally, parenterally, by inhalation spray,topically, rectally, nasally, buccally or via an implanted reservoir.The compounds may also be administered by intracerebral,intracerebroventricular or intrathecal delivery. For parenteraladministration, injections may be given intravenously, intra-arterially,intramuscularly or subcutaneously.

The amount of a compound of the invention to be administered to apatient will vary widely according to the nature of the patient and thenature and extent of the disorder to be treated. Typically the dosagefor an adult human will be in the range of about 0.01 μg/kg to about 1g/kg, preferably about 0.01 mg/kg to about 100 mg/kg. The specificdosage required for any particular patient will depend upon a variety offactors, such as the patient's age, body weight, general health, genderand diet. Optimal doses will depend on other factors such as mode ofadministration and level of progression of the disease or disorder.Doses may be given once daily, or two or more doses may be required perday. For example, a dosage regime for an Alzheimer's patient mightrequire one dose in the morning and one in the evening. Alternatively, adosage regime for such a patient might require four hourly doses.

For oral administration the compounds can be formulated into solid orliquid preparations, for example tablets, capsules, granules, powders,solutions, suspensions, syrups, elixirs and dispersions. Suchpreparations are well known in the art as are other oral dosage regimesnot listed here.

For parenteral administration, compounds of the invention can beformulated into sterile solutions, emulsions and suspension.

Compounds of the invention may be mixed with suitable vehicle and thencompressed into the desired shape and size. The compounds may betableted with conventional tablet bases such as lactose, sucrose andcorn starch, together with a binder, a disintegration agent and alubricant. The binder may be, for example, corn starch or gelatin, thedisintegrating agent may be potato starch or alginic acid, and thelubricant may be magnesium stearate. For oral administration in the formof capsules, diluents such as lactose and dried cornstarch may beemployed. Other components such as colourings, sweeteners or flavouringsmay be added. Tablets, capsules or powders for oral administration maycontain up to about 99% of a compound of the invention.

When liquid preparations are required for oral use, a compound of theinvention may be combined with a pharmaceutically acceptable carrierssuch as water, an organic solvent such as ethanol, or a mixture of both,and optionally other additives such as emulsifying agents, suspendingagents, buffers, preservatives, and/or surfactants may be used.Colourings, sweeteners or flavourings may also be added.

The compounds may also be administered by injection in apharmaceutically acceptable diluent such as water or saline. The diluentmay comprise one or more other ingredients such as ethanol, propyleneglycol, an oil or a pharmaceutically acceptable surfactant.

The compounds of the invention may also be administered topically.Carriers for topical administration of the compounds include mineraloil, liquid petrolatum, white petrolatum, propylene glycol,polyoxyethylene, polyoxypropylene compound, emulsifying wax and water.The compounds may be present as ingredients in lotions or creams, fortopical administration to skin or mucous membranes. Such creams maycontain the active compounds suspended or dissolved in one or morepharmaceutically acceptable carriers. Suitable carriers include mineraloil, sorbitan monostearate, polysorbate 60, cetyl ester wax, cetearylalcohol, 2-octyldodecanol, benzyl alcohol and water.

The compounds of the invention may further be administered by means ofsustained release systems. For example, they may be incorporated into aslowly dissolving tablet or capsule.

Synthesis of the Compounds of the Invention

The compounds of the invention may be prepared by a variety of differentmethods. The following are representative non-limiting general methodsfor synthesising compounds of the invention.

The synthetic strategy involves disaccharide building blocks asintermediates for the preparation of the compounds of the invention. Thepresent invention therefore also relates to intermediates and methodsfor the synthesis of compounds of the invention.

The Disaccharide Building Blocks

The octa- deca- and dodecasaccharide compounds of the invention areprepared from three, four or five neutral disaccharide building blocksof general formula (A) and/or (B), respectively, selected independentlyfor the reducing terminal and internal disaccharide units, and one of(C) or (D) selected independently for the non-reducing terminaldisaccharide unit.

wherein R¹′, R²′, R³′, R⁴′ and R⁷′ are protecting groups chosen withdiffering reactivity so that they can be selectively removed as requiredin the process detailed below, namely R⁴′ before R⁷′ before R¹′ beforeR²′ before R³′.

Ester groups are suitable R¹′, R²′ and R⁷′ protecting groups. The esterprotecting group R²′ facilitates the control of the anomericstereochemistry of the glycosylation reactions to give products with therequired 1,2-trans-stereochemistry with high selectivity.

The acetyl group is a suitable R¹′ protecting group.

The benzoyl group is a suitable R²′ protecting group.

The benzyl group is a suitable R³′ protecting group.

The chloroacetyl group is a suitable R⁷′ protecting group. Themethoxyacetyl and levulinoyl groups are alternative R⁷′ protectinggroups. Levulinoyl groups are described by Wang et al., Chem. J. Eur.,16 (2010) 8365.

The fluorenylmethoxycarbonyl group is a suitable R⁴′ protecting group.

Advantageously and surprisingly, some disaccharide building blocks arecrystalline compounds. This makes them particularly suitableintermediates for the synthesis of compounds of the invention, as theycan be easily stored and transported. The present invention also relatesto such crystalline disaccharide intermediates.

Synthesis of a 4-Methoxyphenyl Glycoside Octasaccharide Compound of theInvention

An octasaccharide compound of the invention is synthesised from threeneutral disaccharide building blocks of general formula (A) and/or (B),respectively, selected independently for the reducing terminal andinternal disaccharide units, and one of (C) or (D) selectedindependently for the non-reducing terminal disaccharide unit.

Stage 1, the First Glycosylation Reaction

The tetrasaccharide (G) is prepared by:

-   -   a) synthesis of an acceptor (E) from a building block (A) or (B)        by selective removal of the protecting group R⁴′;    -   b) synthesis of a glycosyl donor (F) from a building block (A)        or (B) by selective removal of the 4-methoxyphenyl group and        introducing a suitable leaving group at C-1 of the reducing        sugar; and    -   c) coupling of the donor (F) and acceptor (E).

where R⁸′ and R⁹′ are independently chosen from hydrogen and CH₂OR⁷′with the proviso that when one is hydrogen, the other is CH₂OR⁷′.

Selective removal of a fluorenylmethoxycarbonyl protecting group isconveniently achieved by dissolution in mixture of dichloromethane andtriethylamine, typically about 4:1 v/v, 20 mL per mmol, at ambienttemperature, typically in the range of about 10° C. to about 30° C.

Selective removal of the 4-methoxyphenyl group is conveniently achievedby use of CAN.

The trichloroacetimidate group is a suitable leaving group X. Themethylthio, phenylthio and 4-methylphenylthio groups are alternativeleaving groups X.

Glycosyl trichloroacetimidates are conveniently synthesised from thefree-sugar precursors by reaction with excess trichloroacetonitrile anda base. NaH is a suitable base. DBU is alternative base (see WO03/022860). DCM is a suitable solvent and the reaction can be conductedin the range of about −10° C. to about 40° C., preferably about 0° C. toabout 10° C., typically in an ice bath.

Suitable glycosidation conditions are described below.

Syntheses of suitable 1-thioglycoside donors and conditions suitable forglycosylation using them are reported in Wang et al., Chem. J. Eur., 16(2010) 8365 and in WO 03/0228860.

Stage 2, the Second Glycosylation Reaction

The hexasaccharide (H) is prepared by:

-   -   a) synthesis of a tetrasaccharide acceptor by selective removal        of the protecting group R⁴′ from (G) to generate a free        secondary hydroxy group; and    -   b) coupling of the donor (F) from Stage 1 to this        tetrasaccharide acceptor.

where R¹⁰′ and R¹¹′ are independently chosen from hydrogen and CH₂OR⁷′with the proviso that when one is hydrogen, the other is CH₂OR⁷′.

Stage 3, the Third Glycosylation Reaction

The octasaccharide (J) is prepared by:

-   -   a) synthesis of a hexasaccharide acceptor by selective removal        of the protecting group R⁴′ from (H) to generate a free        secondary hydroxy group;    -   b) synthesis of a glycosyl donor (I) from a building block (C)        or (D) by selective removal of the 4-methoxyphenyl group and        introducing a suitable leaving group at C-1 of the reducing        sugar; and    -   c) coupling of the donor (I) with this hexasaccharide acceptor.

where R¹²′ and R¹³′ are independently chosen from hydrogen and CH₂OR⁷′with the proviso that when one is hydrogen, the other is CH₂OR⁷′.

Stage 4, Conversion to Final Product

The octasaccharide of the invention is prepared by:

-   -   a) selective removal of all protecting groups R⁷′ from the        neutral octasaccharide derivative (J);    -   b) oxidation of all the resulting free primary hydroxy groups to        the corresponding carboxylic acid groups (or salt forms        thereof);    -   c) conversion of all the carboxylic acid moieties into their        corresponding methyl esters;    -   d) converting all the azide-groups into the corresponding        acylamino-groups;    -   e) selective removal of all R¹′ protecting groups;    -   f) sulfation of the resulting primary hydroxy groups;    -   g) selective removal of all R²′ protecting groups and hydrolysis        of the methyl esters;    -   h) sulfation of the resulting secondary hydroxy groups, or        proceeding directly to step i);    -   i) removal of the R³′ protecting groups; and    -   j) conversion to the desired cationic salt form of the final        product.

Selective removal of the chloroacetyl R⁷′ protecting group isconveniently achieved using DABCO (6 equiv. per chloroacetyl group) indry ethanol heated at about 60° C. to about 70° C. under argon.

Oxidation of the resulting free primary hydroxy group is convenientlyachieved using the TEMPO-BAIB system in aqueous acetonitrile at roomtemperature. Conversion of the resulting carboxylic acid intocorresponding methyl ester is conveniently achieved by reaction withdiazomethane, TMS-diazomethane, or a combination of iodomethane and abase, conveniently potassium bicarbonate, in DMF. An alternative TEMPOoxidation system is described in WO 03/022860.

Conversion of the azido-group into the corresponding acetamido-group isconveniently achieved by reaction with thiolacetic acid in dry pyridineat room temperature. Conversion of the azido-group into an alternativeacylamido-group is achieved by reduction of the azido-group,conveniently with trialkylphosphine (e.g. nBu₃P), triarylphosphine (e.g.Ph₃P), or a metal catalyst (e.g. Pd/C) and reaction, either in the samereaction mixture or separately, with an acylating agent (e.g. an acylanhydride or an acyl chloride).

Selective removal of the acetyl R¹′ protecting group is convenientlyachieved using HCl in a DCM-MeOH solution in the temperature range ofabout 0° C. to about 30° C. The HCl can be generated in situ by use ofacetyl chloride.

Cleavage of ester R²′ protecting groups is conveniently conducted bysaponification with sodium hydroxide in aqueous methanol.

Sulfation reactions are conveniently conducted using sulfur trioxidetrimethylamine complex (5 equiv per hydroxyl group) in dry DMF at about50° C. to about 60° C. under argon.

Removal of the benzyl R³′ protecting group is conveniently conductedusing hydrogen and a palladium catalyst, typically palladium hydroxideon carbon, in aqueous tetrahydrofuran in the range of about 10° C. toabout 30° C.

Final products are converted into the desired salt form by elution withwater through a Strong acid ion exchange resin column, e.g. Dowex50WX8-200 (Dow Chemical Company, USA) in the desired salt form, e.g.Na⁺.

Synthesis of a 4-Methoxyphenyl Glycoside Decasaccharide of the Invention

A decasaccharide compound of the invention is synthesised from fourneutral disaccharide building blocks of general formula (A) and/or (B),respectively, selected independently for the reducing terminal andinternal disaccharide units, and one of (C) or (D) selectedindependently for the non-reducing terminal disaccharide unit.

Thus, the octasaccharide (K) is prepared by:

-   -   a) synthesis of a hexasaccharide acceptor by selective removal        of the protecting group R⁴′ from hexasaccharide derivative (H)        to generate a free secondary hydroxy group;    -   b) coupling of the donor (F) with this hexasaccharide acceptor.

Then decasaccharide (L) is prepared by:

-   -   a) synthesis of an octasaccharide acceptor by selective removal        of the protecting group R⁴′ from octasaccharide derivative (K)        to generate a free secondary hydroxy group;    -   b) coupling of the donor (I) with this octasaccharide acceptor.

where R¹⁴′ and R¹⁵′ are independently chosen from hydrogen and CH₂OR⁷′with the proviso that when one is hydrogen, the other is CH₂OR⁷′.

Finally, the decasaccharide of the invention is prepared by:

-   -   a) selective removal of all protecting groups R⁷′ from the        neutral decasaccharide derivative (L);    -   b) oxidation of all the resulting free primary hydroxy groups to        the corresponding carboxylic acid groups (or salt forms        thereof);    -   c) conversion of all the carboxylic acid moieties into their        corresponding methyl esters;    -   d) converting all the azido-groups into the corresponding        acylamino-groups;    -   e) selective removal of all R¹′ protecting groups;    -   f) sulfation of the resulting primary hydroxy groups;    -   g) selective removal of all R²′ protecting groups and hydrolysis        of the methyl esters;    -   h) sulfation of the resulting secondary hydroxy groups or        proceeding directly to step (i).    -   i) removal of the R³′ protecting groups; and    -   j) conversion to the desired cationic salt form of the final        product.

Synthesis of a 4-Methoxyphenyl Glycoside Dodecasaccharide of theInvention

A dodecasaccharide compound of the invention is synthesised from fiveneutral disaccharide building blocks of general formula (A) and/or (B),respectively, selected independently for the reducing terminal andinternal disaccharide units, and one of (C) or (D) selectedindependently for the non-reducing terminal disaccharide unit.

Thus, the decasaccharide (M) is prepared by:

-   -   a) synthesis of an octasaccharide acceptor by selective removal        of the protecting group R⁴′ from octasaccharide derivative (K)        to generate a free secondary hydroxy group;    -   b) coupling of the donor (F) with this octasaccharide acceptor.

Then dodecasaccharide (N) is prepared by:

-   -   a) synthesis of an decasaccharide acceptor by selective removal        of the protecting group R⁴′ from octasaccharide derivative (M)        to generate a free secondary hydroxy group;    -   b) coupling of the donor (I) with this octasaccharide acceptor.

where R¹⁶′ and R¹⁷′ are independently chosen from hydrogen and CH₂OR⁷′with the proviso that when one is hydrogen, the other is CH₂OR⁷′.

Finally, the dodecasaccharide of the invention is prepared by:

-   -   a) selective removal of all protecting groups R⁷′ from the        neutral decasaccharide derivative (N);    -   b) oxidation of all the resulting free primary hydroxy groups to        the corresponding carboxylic acid groups (or salt forms        thereof);    -   c) conversion of all the carboxylic acid moieties into their        corresponding methyl esters;    -   d) converting all the azido-groups into the corresponding        acylamino-groups;    -   e) selective removal of all R¹′ protecting groups;    -   f) sulfation of the resulting primary hydroxy groups;    -   g) selective removal of all R²′ protecting groups and hydrolysis        of the methyl esters;    -   h) sulfation of the resulting secondary hydroxy groups or        proceeding directly to step i).    -   i) removal of the R³′ protecting groups; and    -   j) conversion to the desired cationic salt form of the final        product.

Synthesis of Alternative Compounds of the Invention

An octa- deca- or dodecasaccharide compound of the invention having anoptionally substituted alkyl, aralkyl or aryl aglycone is synthesised byselective cleavage of the 4-methoxyphenyl residue from C-1 of thereducing sugar moiety on a hexasaccharide derivative (K) or thedecasaccharide moiety (L) or the dodecasaccharide moiety (N),respectively, and introducing a suitable leaving group at C-1 of thereducing sugar and then coupling the resulting oligoglycosyl donor withan optionally substituted alkyl, aralkyl or aryl alcohol. Thestereochemistry of the newly formed anomeric centre is typically betadue to neighbouring group participation by the adjacent R²′ esterprotecting group in the glycosidation reaction.

In an alternative approach, an octa- or deca- or dodecasaccharidecompound of the invention having an optionally substituted alkyl,aralkyl or aryl aglycone is synthesised by substituting the disaccharidebuilding block (P) for the disaccharide building block (E) that providesthe reducing sugar disaccharide moiety in a octa- deca- ordodecasaccharide of the invention in the processes outlined above (under“synthesis of a 4-methoxyphenyl glycoside octasaccharide of theinvention”, “synthesis of a 4-methoxyphenyl glycoside decasaccharide ofthe invention” and “synthesis of a 4-methoxyphenyl glycosidedodecasaccharide of the invention”).

where R^(A)′ and R^(B)′ are chosen from an optionally substitutedalkyloxy, aralkyloxy or aryloxy group and hydrogen, with the provisothat when one is hydrogen, the other is an optionally substitutedalkyloxy, aralkyloxy or aryloxy group.

A disaccharide building block (P) is conveniently synthesised byreaction of the glycosyl donor (F) with the desired optionallysubstituted alkyl, aralkyl or aryl alcohol. As the R²′ is a esterprotecting group, the product is usually the beta-anomer (in whichR^(A)′ is hydrogen).

Synthesis of the Disaccharide Building Blocks

The neutral disaccharide building blocks of general formula (A) and (B)are synthesised by coupling a glycosyl donor of formula (Q) with amonosaccharide acceptor of formula (S) or (T), respectively.

The neutral disaccharide building blocks of general formula (C) and (D)are synthesised by coupling a glycosyl donor of formula (R) with amonosaccharide acceptor of formula (S) or (T), respectively.

The required 1,2-cis-configuration at C-1 and C-2 of the non-reducingsugar residue in the disaccharide building blocks (A), (B), (C) and (D)is attained by suitable choice of leaving group X and glycosidationreagent. Suitable choices of X and glycosidation reagent areX=beta-(methylthio)-, beta-(phenylthio)- or beta-(4-methylthio)-, withthe combination of N-iodosuccinimide and silver triflate asglycosidation reagents.

Typical Glycosidation Reaction Conditions

For the glycosidation reactions in which a disaccharide (A), (B), (C) or(D), a tetrasaccharide (G), a hexasaccharide (H), an octasaccharide (J)or (K), or a decasaccharide (L) or (M), or a dodecasaccharide (N), issynthesised, the donor is conveniently used in a molar ratio to theacceptor in the range 1.0 to 1.5 equivalents, preferably in a rangebetween 1.05 and 1.5 equivalents, preferably 1.2 to 1.3 equivalents,preferably 1.3 equivalents.

Conveniently the glycosyl donor is a glycosyl trichloroacetimidate.Reactions with acceptor alcohols are conveniently carried out inanhydrous toluene (40 mL per mmol acceptor) at between −10 and 40° C.,in the presence of powdered molecular sieves (4 Å) and trimethylsilyltrifluoromethanesulfonate (0.3 eq).

Abbreviations

NMR Nuclear magnetic resonance

TLC Thin layer chromatography

RT Room temperature

DCM Dichloromethane

Ac Acetyl

AcOH Acetic acid

BAIB Bis(acetoxy)iodobenzen

Bn Benzyl

Bz Benzoyl

CAN Ceric ammonium (IV) nitrate

ClAc Chloroacetyl

DABCO 1,4-Diazabicyclo[2.2.2]octane

DMAP 4-N,N-Dimethylaminopyridine

DMF N,N-Dimethylformamide

ESI Electrospray ionization

EtOAc Ethyl acetate

Fmoc Fluorenylmethoxycarbonyl

Fmoc-Cl Fluorenylmethoxycarbonyl chloride

HSQC Heteronuclear single quantum correlation

HRMS High resolution mass spectrum

gl.AcOH Glacial acetic acid

MeOAc Methoxyacetyl

MeOH Methanol

MS Mass spectrum

NBS N-Bromosuccinimide

NI N-Iodosuccinimide

TEMPO 2,2,6,6-Tetramethyl-1-piperidinyloxyl

TFA Trifluoroacetic acid

THF Tetrahydrofuran

TMS-diazomethane Trimethylsilylmethyl diazomethane

EXAMPLES

The following examples further illustrate the invention. It is to beappreciated that the invention is not limited to the examples.

Example 1 Synthesis of Compounds

Preparation of 1

Methyl 2-azido-2-deoxy-1-thio-β-D-glucopyranoside (Pozsgay, V.;Glaudemans, C. P. J.; Robbins, J. B.; Schneerson, R. Tetrahedron 1992,48, 10249-10264) (20 g, 85 mmol) is dissolved in 200 mL dry pyridine.Trityl chloride (30 g, 108 mmol) is added and the mixture stirredovernight. More trityl chloride (2 g) is added and stirring continuedfor 3 h until TLC (petroleum ether/ethyl acetate 1:1) confirmscompletion. The mixture is concentrated in vacuo, coevaporated withtoluene (2×150 mL), washed with CuSO4, water, brine, concentrated todryness and coevaporated with DCM to an off-white foam. This isdissolved in dry DMF (100 mL), cooled in an ice-bath and benzyl bromide(30.3 ml, 255 mmol) is added, followed by sodium hydride 60% (11.22 g,281 mmol) in portions, the ice-bath is removed after addition of thefirst 2 g of NaH. After stirring at room temperature for 1 h, thereaction is again cooled in an ice-bath and quenched by addition ofethanol, then diluted with 500 mL toluene, washed with water (3×1000mL), brine (300 mL) and dried over magnesium sulfate. Solvents areevaporated and the resulting syrup is coevaporated with dichloromethane,the residue is taken up in toluene and crytallised by addition ofmethanol. The solids are collected, washed with methanol and dried undervacuum to give the benzyl/trityl-derivative 1 in 94% yield (52.3 g, 80mmol) as a white powder. ¹³C-NMR (125 MHz, CDCl₃) δ 143.9, 137.8, 137.6,129.1, 128.8. 128.6, 128.3, 128.2, 128.1, 127.9, 127.8, 127.1, 86.5,85.0, 84.0, 79.1, 77.8, 76.0, 75.0, 65.8, 62.4, 11.9

Preparation of 2

Tritylated compound 1 (55.3 g, 84 mmol) is combined with acetic acid(300 mL), water (80 mL) is added and the mixture heated to 80° C. for 8h. The reaction mixture is concentrated and the product crystallisesfrom ethyl acetate (100 mL) by addition of petroleum ether in 80% yield(27.8 g, colourless crystals). The obtained alcohol is dissolved inpyridine/acetic anhydride 2:1 (300 mL) and stirred for 6 h at ambienttemperature, subsequently the solvents are evaporated to a syrup, whichcrystallises on standing and is triturated with petrol (450 mL) for 3 d.Solids are collected and dried under vacuum to give 2 (27.1 g, 65.2mmol) as a white powder. ¹³C-NMR (125 MHz, CDCl₃) δ 170.6, 137.6, 137.4,128.6, 128.5, 128.4, 128.1, 128.0, 127.8, 85.1, 84.5, 76.8, 65.7, 63.00,20.8, 12.5

Preparation of 3

Methyl 2-azido-4,6-di-O-benzylidene-2-deoxy-1-thio-β-D-glucopyranoside(Rajaratnam, P.; Gupta, P.; Katavic, P.; Kuipers, K; Huyh, N.; Ryan, S.;Falzun, T.; Tometzki, G. B.; Bornaghi, L.; Le Thanh, G.; Abbenante, G.;Liu, L.; Meutermans, W.; Wimmer, N.; West, M. L. Aust. J. Chem. 2010,63, 693-699. Dekany, G.; Alchemia Pty. Ltd., US Patent Publication, U.S.Pat. No. 6,953,850 B1, 2005) (62.1 g, 192 mmol) is dissolved in dry DMF(150 mL), benzyl bromide (27.4 ml, 230 mmol) is added and cooled in anice bath. Then sodium hydride 60% (9.99 g, 250 mmol) is addedportion-wise and the reaction stirred at room temperature until TLCshows full conversion to a less polar product. The reaction is quenchedwith MeOH, then evaporated under high vacuum. Chloroform is added to theresidue and washed three times with water and dried over magnesiumsulfate to give a solid residue. Then diethyl ether is added to dissolvea part of the solids and precipitated with petroleum ether. Solids arecollected and washed with petroleum ether to yield an off-white solid(56.7 g) Evaporation of the mother liquor, followed by trituration withether/petroleum ether gives more yellow solid, (12.67 g). Total ofbenzyl ether 3 68.37 g, 86%. ¹³C-NMR (125 MHz, CDCl₃) δ 137.7, 137.2,129.1, 128.5, 128.4, 128.3, 128.0, 126.0, 101.3, 85.2, 81.6, 80.9, 75.1,70.5, 68.5, 65.3, 12.7

Preparation of 4

Dioxane (125 mL) and methanol (400 mL) are added to benzyl ether 3 (68.3g, 165 mmol) and the mixture is stirred at room temperature. Acetylchloride (8 mL, 113 mmol) is added and the reaction mixture is stirredat room temperature for 1.5 h, until TLC shows full conversion. Thereaction is neutralized with Amberlyst A26 (OH—) resin, filtered and thefiltrate evaporated to dryness. Silica chromatography (EtOAc/Hex1:2-3:2) gives a pale yellow syrup that crystallizes: methyl2-azido-3-O-benzyl-2-deoxy-1-thio-β-D-glucopyranoside 4 49.14 g, 91%.¹³C-NMR (125 MHz, CDCl₃) δ 137.9, 128.7, 128.5, 128.3, 128.1, 127.8,84.9, 84.5, 79.5, 75.4, 70.1, 65.2, 62.0, 12.7

Preparation of 5

Compound 4 (47.9 g, 147 mmol) is dissolved in dry dichloromethane (590mL), Pyridine (71.4 ml, 883 mmol) is added and cooled to −75° C. Acetylchloride (10.47 ml, 147 mmol) is added slowly and the reaction isallowed to warm up to room temperature over night. TLC confirms completeconversion and the reaction mixture is washed with 10% HCl, aq. sodiumbicarbonate and brine (400 mL resp.), dried over magnesium sulfate,concentrated and dissolved in hot toluene (100 ml). The productcrystallises in the fridge (4° C.), is collected by filtration, washedwith petroleum ether and dried under oil-pump vacuum: methyl6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-1-thio-β-D-glucopyranoside 5 (50g, 92% yield). ¹³C-NMR (125 MHz, CDCl₃) δ 171.7, 137.8, 128.7, 128.6,128.2, 127.9, 127.7, 84.7, 84.2, 77.9, 75.5, 70.1, 65.2, 63.2, 20.8,12.5

Preparation of 6

DMAP (700 mg, 5.73 mmol) is added to a solution of 5 (50 g, 136 mmol) inanhydrous pyridine (100 ml) and cooled in an ice-bath. Fmoc-Cl (141 g,544 mmol) is added and the ice-bath is removed after 15 min. Theresulting suspension is stirred at room temperature for 1.5 h. Thesolvents are evaporated and the residue is purified by repeated silicachromatography (toluene/ethyl acetate 4%); clean fractions are combinedand co-evaporated with dichloromethane to form a foam: methyl6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-4-O-(9-fluorenylmethyloxycarbonyl)-1-thio-β-D-glucopyranoside6 (69 g, 117 mmol, 86% yield). R_(f)=0.15 (toluene/ethyl acetate 19:1),¹³C-NMR (125 MHz, CDCl₃) δ 170.6. 154.2, 143.2, 143.0, 141.3, 137.1,128.4, 128.0, 127.2, 125.1, 124.9, 120.1, 84.6, 82.1, 75.7, 75.5, 74.3,70.3, 65.1, 62.3, 46.8, 20.7, 12.4

Ido-Configured Monosaccharide Building Block Synthesis 01

Reaction of a known tetra-benzoate (Barroca, N.; Jacquinet, J.-C. 2000,Carbohydr. Res., 329, 667-679) with 4-methoxyphenol and subsequentZemplen deacetylation affords a triol 7. Isopropylidenation gives thecompound 8. Benzylation afforded a benzoate 9. Acidic hydrolysis gives adiol 10. Selective chloroacetylation furnishes a mono-chloroacetateacceptor 11.

Synthesis of 7

A solution of tetra-benzoate (Barroca, N.; Jacquinet, J.-C. 2000,Carbohydr. Res., 329, 667-679) (56.2 g, 82 mmol) in dry dichloromethane(400 mL) is treated with 4-methoxyphenol (2 equiv., 20.3 g, 164 mmol)and boron trifluoride diethyl etherate (0.5 equiv., 5 ml, 40.9 mmol) andstirred at room temperature for 2 hours. Then the reaction mixture iswashed with saturated aq. sodium bicarbonate twice, dried andconcentrated. The residue is dissolved in dry methanol (500 mL) andtreated with 25% solution of sodium methoxide (15 mL) and stirred atroom temperature for 18 hours. The reaction mixture is neutralized withion-exchange resin (Amberlyst-H⁺) and the resin is filtered off. Theresidue is purified by silica gel chromatography (EtOAc:petroleum ether,1:2) to furnish the triol 7 as a syrup: 25.0 g (81%), R_(f)=0.15(EtOAc:petroleum ether, 1:1). HRMS (ESI) calcd for C₂₀H₂₄O₇Na(M+Na)⁺ m/z399.142, found 399.1421. ¹H-NMR (500 MHz, CDCl₃) δ 7.39-7.23 (m, 5 H),6.99 (d, J=9.1 Hz, 2H), 6.82 (d, J=9.2 Hz, 2H), 5.53 (d, J=4.5 Hz, 1H),4.79 (d, J=12.4 Hz, 1H), 4.58 (d, J=11.9 Hz, 1H), 4.23 (d, J=8.8 Hz,1H), 4.07 (dd, J=4.0, J=12.1, 1H), 3.89-3.83 (m, 3H), 3.81 (d, J=9.5,1H), 3.74 (s, 3H); ¹³C-NMR (CDCl₃) δ 154.9, 150.7, 138.0, 133.3, 130.1,129.9, 128.5, 127.8, 127.6, 123.2, 117.9, 114.7, 100.4, 75.1, 71.7,70.8, 66.1, 65.1, 60.5, 55.7.

Synthesis of 8

A solution of 7 (17 g, 45.2 mmol) in dry DMF (150 mL) is treated with2,2-dimethoxypropane (100 mL) and p-toluenesulfonic acid monohydrate(100 mg) and stirred at room temperature for 5 hours. Then the reactionmixture is diluted with ethyl acetate, washed with saturated aq. sodiumbicarbonate and water, dried and concentrated. The residue is purifiedby silica gel chromatography (EtOAc:petroleum ether, 1:2) to afford theisopropylidene derivative 8 as a syrup: 17.9 g, 43 mmol (95%),R_(f)=0.75 (EtOAc:petroleum ether, 1:1). HRMS (ESI) calcd forC₂₃H₂₈O₇Na(M+Na)⁺ m/z 439.1733, found 439.1725. ¹H-NMR (500 MHz, CDCl₃)δ 7.43-7.29 (m, 5 H), 7.04 (d, J=9.2 Hz, 2H), 6.82 (d, J=9.1 Hz, 2H),5.59 (d, J=5.3 Hz, 1H), 4.8 (d, J=11.8 Hz, 1H), 4.62 (d, J=11.1 Hz, 1H),4.08 (d, J=8.5 Hz, 1H), 4.03-3.97 (m, 3H), 3.81 (dd, J=4.2, J=12.3, 1H),3.75 (s, 3H), 3.61 (d, J=11.2 Hz, 1H), 1.47 (s, 3H), 1.44 (s, 3H);¹³C-NMR (125 MHz, CDCl₃) δ 154.7, 150.9, 137.9, 128.5, 127.9, 127.7,117.4, 114.6, 99.6, 99.3, 74.9, 71.7, 68.2, 65.2, 63.1, 60.5, 60.4,55.7, 29.3, 18.5.

Synthesis of 9

A solution of 8 (17 g, 40.8 mmol) in dry dichloromethane (100 mL) anddry pyridine (50 mL) is treated with benzoyl chloride (2 equiv., 9.48mL, 82 mmol) at 0° C. The reaction mixture is stirred at 0° C. for 30min followed by stirring at room temperature for 5 hours. Then themixture is diluted with ethyl acetate and washed with saturated aq.sodium bicarbonate and water, dried and concentrated. The residue ispurified by silica gel chromatography (EtOAc:petroleum ether, 1:3) toafford the benzoate 9 as a syrup: 20.0 g, 38.4 mmol (95%), R_(f)=0.4(EtOAc:petroleum ether, 1:2). HRMS (ESI) calcd for C₃₀H₃₂O₈Na(M+Na)⁺ m/z543.1995, found 543.1985. ¹H-NMR (500 MHz, CDCl₃) δ 8.14 (d, J=7.6 Hz,2H), 7.56-7.52 (m, 1 H), 7.43-7.38 (m, 4 H), 7.34-7.28 (m, 3 H), 7.05(d, J=9.2 Hz, 2H), 6.81 (d, J=9.1 Hz, 2H), 5.68 (d, J=6.1 Hz, 1H), 5.49(dd, J=2.5 Hz, J=6.2 Hz, 1H), 4.94 (d, J=11.4 Hz, 1H), 4.72 (d, J=11.5Hz, 1H), 4.12-4.04 (m, 3H), 3.91 (dd, J=4.3, J=13.1, 1H), 3.82 (t,J=7.2, 1H), 3.74 (s, 3H), 3.61 (d, J=11.2 Hz, 1H), 1.49 (s, 3H), 1.45(s, 3H); ¹³C-NMR (125 MHz, CDCl₃) δ 165.5, 154.9, 150.7, 137.9, 133.5,133.3, 130.1, 130.0, 129.8, 129.5, 128.4, 128.3, 127.8, 117.6, 114.6,98.75, 97.55, 75.1, 72.1, 67.7, 67.1, 62.7, 61.1, 60.4, 55.7, 28.9,18.9.

Synthesis of 10

A solution of 9 (20 g, 38.4 mmol) in gl.AcOH (160 mL) and water (80 mL)is stirred at 80° C. for 1 hour. Then the solvents are removed in vacuoand the residue is purified by silica gel chromatography(EtOAc:petroleum ether, 1:1) to give the diol 10 as a foam, 16.0 g, 33.3mmol (87%), R_(f)=0.15 (EtOAc:petroleum ether, 1:2). HRMS (ESI) calcdfor C₂₇H₂₈O₈Na(M+Na)⁺ m/z 503.1682, found 503.1689. ¹H-NMR (500 MHz,CDCl₃) δ 8.04 (d, J=7.6 Hz, 2H), 7.61-7.56 (m, 1 H), 7.47-7.39 (m, 4 H),7.36-7.27 (m, 3 H), 7.05 (d, J=9.2 Hz, 2H), 6.83 (d, J=9.1 Hz, 2H), 5.57(bs, 1H), 5.47-5.45 (m, 1H), 4.93 (d, J=12.0 Hz, 1H), 4.70 (d, J=11.5Hz, 1H), 4.47-4.44 (m, 1H), 3.94-3.88 (m, 2H), 3.85-3.80 (m, 1H), 3.75(s, 3H); ¹³C-NMR (125 MHz, CDCl₃) δ 171.2, 165.1, 155.2, 150.4, 137.8,133.7, 129.8, 129.2, 128.7, 128.5, 127.9, 127.7, 118.3, 114.7, 97.9,75.2, 72.0, 68.4, 68.1, 67.9, 63.2, 60.4, 55.6.

Synthesis of 11

A solution of 10 (15 g, 31.2 mmol) in dry dichloromethane (100 mL) anddry pyridine (20 mL) is treated with a solution of chloroacetyl chloride(0.85 equiv., 2.11 mL, 26.5 mmol) in dry dichloromethane (5 mL) dropwiseat −78° C. The reaction mixture is stirred at −78° C. for 45 min,allowed to warm up to 0° C. and quenched with water (5 mL). Then themixture is diluted with dichloromethane, washed with saturated aq.sodium bicarbonate and water, dried and concentrated. The residue ispurified by silica gel chromatography (EtOAc:petroleum ether, 1:3) toafford the chloroacetate 11 as a foam, 15.0 g, 26.9 mmol (86%),R_(f)=0.35 (EtOAc:petroleum ether, 1:2). HRMS (ESI) calcd forC₂₉H₂₉O₉ClNa(M+Na)⁺ m/z 579.1398, found 579.1395. ¹H-NMR (500 MHz,CDCl₃) δ 8.03 (d, J=7.5 Hz, 2H), 7.62-7.59 (m, 1 H), 7.49-7.41 (m, 3 H),7.39-7.35 (m, 2 H), 7.33-7.29 (m, 1 H), 7.05 (d, J=10.0 Hz, 2H), 6.85(d, J=8.9 Hz, 2H), 5.56 (bs, 1H), 5.47-5.45 (m, 1H), 4.95 (d, J=11.8 Hz,1H), 4.70 (d, J=11.8 Hz, 1H), 4.66-4.63 (m, 2H), 4.55-4.51 (m, 1H),4.35-4.31 (m, 1H), 3.93-3.91 (m, 1H), 3.85 (s, 2H); 3.78 (s, 3H);¹³C-NMR (125 MHz, CDCl₃) δ 166.9, 164.9, 155.3, 150.1, 137.6, 133.8,129.8, 128.9, 128.8, 128.5, 127.9, 127.8, 118.3, 114.6, 97.3, 74.7,72.1, 67.5, 67.1, 66.3, 65.2, 60.4, 55.7, 40.8.

Preparation of 12

Pyridine (0.447 ml, 5.53 mmol) is added to p-methoxyphenyl2-O-benzoyl-3-O-benzyl-β-D-glucopyranoside (Karst, N.; Jacquinet, J.-C.2002, Eur. J. Org. Chem., 815-825) (0.443 g, 0.922 mmol) in drydichloromethane (5 mL) and cooled to −75° C. Chloroacetyl chloride(0.074 ml, 0.922 mmol) (1.0 mL of a solution of 0.74 mL in 9.3 mL ofDCM) is added slowly and the reaction is kept in cold bath for 1 h, thenwater (1 mL) is added and warmed to RT. The reaction mixture is washedwith water, dil. HCl, aq. sodium bicarbonate and dried over magnesiumsulfate. Evaporation of solvents gives a white solid whichrecrystallises from EtOAc/hexanes: alcohol 12, 0.41 g, 80%. ¹³C-NMR (75MHz, CDCl₃) δ 167.8, 165.6, 156.1, 151.6, 138.0, 133.7, 130.2, 130.0,129.0, 128.9, 128.5, 119.2, 114.9, 101.3, 82.6, 75.1, 73.9, 73.8, 70.3,65.1, 56.0, 41.1

General Procedure A (GPA): Disaccharide Building Block Synthesis.Thioglycoside donor (1.5 eq) and alcohol (1.0 eq) are dissolved in amixture of anhydrous toluene and anhydrous dichloromethane (25 mL permmol acceptor) and cooled to −15° C. and powdered molecular sieves (4 Å)are added. After 10 min N-iodosuccinimide (1.7 eq) and silvertrifluoromethanesulfonate (0.4 eq) are added. The reaction mixture isallowed to warm up to room temperature over 1 h. The mixture is dilutedwith ethyl acetate and filtered through celite. The filtrate is washedwith a 1:1 mixture of saturated aq. sodium bicarbonate and aq.thiosulfate (30%), washed with saturated aq. sodium chloride, dried overmagnesium sulfate and concentrated. The residue is purified by flashchromatography or crystallisation.

Synthesis of 13

Compound 13 is prepared from compound 12 and compound 6 according togeneral procedure A1: 11.2 g (71% crystalline α-anomer), crystallisedfrom hot toluene (60 mL) after addition of petroleum ether. ¹³C-NMR (125MHz, CDCl₃) δ 170.5, 169.9, 165.1, 155.7, 154.2, 151.0, 143.2, 143.0,141.3, 137.3, 137.1, 135.5, 129.6, 129.5, 129.0, 128.9, 128.6, 128.5,128.4, 128.2, 128.0, 127.9, 127.7, 127.2, 125.3, 125.1, 124.9, 120.1,118.7, 114.6, 100.0, 97.9, 82.5, 75.1, 74.8, 74.7, 74.1, 73.5, 72.4,70.4, 68.8, 64.9, 62.6, 62.0, 55.7, 46.7, 40.6, 20.7

Synthesis of 14

Compound 14 is prepared from compound 12 and compound 2 according togeneral procedure A1: 1.11 g (79% α-anomer), crystallised from tolueneafter addition of petroleum ether. ¹³C-NMR (125 MHz, CDCl₃) δ 170.5,166.9, 165.1, 155.7, 151.0, 137.5, 137.4, 137.2, 133.5, 129.8, 129.5,129.1, 129.0, 128.8, 128.6, 128.5, 128.4, 128.1, 128.0, 127.8, 125.3,118.7, 114.5, 100.1, 98.1, 82.7, 80.1, 79.5, 77.9, 75.5, 75.3, 74.9,74.7, 74.2, 73.6, 72.4, 70.4, 64.9, 63.2, 62.6, 55.6, 40.4, 20.7

Synthesis of 15

Compound 15 is prepared from compound 2 and p-methoxyphenyl2-O-benzoyl-3-O-benzyl-6-O-methoxyacetyl-β-D-glucopyranoside accordingto general procedure A1: 850 mg (79% α-anomer), crystallised fromtoluene after addition of petroleum ether. ¹³C-NMR (125 MHz, CDCl₃) δ170.5, 169.9, 165.1, 155.7, 151.1, 137.6, 137.4, 137.2, 133.4, 129.8,129.5, 129.0, 128.6, 128.5, 128.2, 128.1, 128.0, 127.8, 127.7, 125.3,118.8, 114.5, 100.2, 98.0, 82.8, 80.1, 77.9, 75.5, 75.2, 74.5, 74.2,73.7, 72.6, 70.3, 69.5, 63.5, 63.2, 62.6, 59.4, 55.6, 20.8

Synthesis of 16

Compound 16 is prepared from compound 11 and compound 6 according togeneral procedure A: 7.7 g (89%) crystalline α-anomer, R_(f)=0.45(EtOAc:petroleum ether, 1:2). Crystallised from hot ethyl acetate (80mL) after addition of petroleum ether (20%). HRMS (ESI) calcd forC₅₉H₅₆ClN₃O₁₆Na(M+Na)⁺ m/z 1120.3247, found 1120.3246. ¹H-NMR (500 MHz,CDCl₃) δ 8.18 (dd, J=3.7 Hz, J=9.9 Hz, 2 H), 7.79 (d, J=8.6 Hz, 2H),7.61 (d, J=8.6 Hz, 1H), 7.56 (d, J=7.5 Hz, 1H), 7.47-7.42 (m, 4H),7.41-7.35 (m, 3H), 7.33-7.26 (m, 4H), 7.18-7.15 (m, 3H), 7.06 (d, J=9.1Hz 2H), 7.03-6.99 (m, 3H), 6.86 (d, J=10.1 Hz 2H), 5.63 (d, J=4.1 Hz,1H), 5.38 (d, J=3.9 Hz, 1H), 5.03 (d, J=12.1 Hz, 1H), 4.18 (d, J=12.1Hz, 2H), 4.77 (t, J=9.9 Hz, 1H), 4.66 (d, J=4.3 Hz, 1H), 4.61-4.58 (m,3H), 4.56-4.52 (m, 1H), 4.51-4.47 (m, 1H), 4.33-4.27 (m, 1H), 4.25-4.20(m, 1H), 4.19-4.15 (m, 1H), 4.10 (d, J=3.3 Hz, 1H), 4.09-4.05 (m, 1H),4.01 (d, J=11.0 Hz, 3H), 3.85 (d, J=2.5, 2H), 3.77 (s, 3H), 3.72 (d,J=7.3 Hz, 1H), 3.65 (t, J=10.2 Hz, 1H), 3.36-3.33 (m, 1H), 2.01 (s, 3H);¹³C-NMR (125 MHz, CDCl₃) δ 170.5, 166.9, 165.6, 155.3, 154.2, 150.1,143.2, 143.1, 141.3, 137.6, 137.1, 133.5, 129.9, 129.8, 128.7, 128.5,128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.2, 125.1, 124.9, 120.1,118.3, 114.6, 98.9, 97.6, 78.3, 75.7, 75.0, 74.5, 72.4, 72.3, 70.3,68.9, 68.1, 65.6, 65.0, 63.3, 62.1, 55.7, 46.7, 40.5, 20.6.

Synthesis of 17

Compound 17 is prepared from compound 11 and compound 2 according togeneral procedure A: . The residue is purified by silica gelchromatography (EtOAc:petroleum ether, 1:3) to furnish the disaccharideas a foam, 3.7 g (93%), α-anomer, R_(f)=0.45 (EtOAc:petroleum ether,1:2). HRMS (ESI) calcd for C₅₁H₅₂ClN₃O₁₄Na(M+Na)⁺ m/z 988.3036, found988.3043. ¹H-NMR (500 MHz, CDCl₃) δ 8.16 (d, J=8.1 Hz, 2 H), 7.46 (d,J=7.9 Hz, 2 H), 7.42 (d, J=7.1 Hz, 2 H), 7.39-7.34 (m, 3H), 7.33-7.28(m, 5H), 7.26-7.22 (m, 4H), 7.16 (dd, J=7.5 Hz, J=12.3 Hz, 2H), 7.05 (d,J=10.1 Hz, 2H), 6.85 (d, J=9.3 Hz, 2H), 5.61 (d, J=4.0 Hz, 1H), 5.35 (d,J=3.7 Hz, 1H), 5.02 (d, J=12.1 Hz, 1H), 4.81 (d, J=12.2 Hz, 2H), 4.75(d, J=10.8 Hz, 2H), 4.64 (d, J=4.3 Hz, 2H), 4.59-4.55 (m, 3H), 4.53-4.51(m, 1H), 4.50-4.48 (m, 1H), 4.35-4.30 (m, 1H), 4.29 (d, J=3.0 Hz, 1H),4.29 (d, J=3.0 Hz, 1H), 4.27 (d, J=3.0 Hz, 1H), 4.21-4.17 (m, 1H), 4.13(d, J=8.0 Hz, 2H), 4.10 (d, J=10.0 Hz, 2H), 3.94-3.91 (m, 1H), 3.84 (d,J=4.8, 2H), 3.77 (s, 3H), 3.72-3.69 (m, 1H), 3.65 (t, J=10.2 Hz, 1H),3.39 (t, J=9.2 Hz, 1H), 3.31 (dd, J=6.5 Hz, J=12.9 Hz, 1H), 2.0 (s, 3H);¹³C-NMR (125 MHz, CDCl₃) δ 170.5, 166.8, 165.6, 155.2, 150.2, 137.6,137.4, 137.3, 133.3, 129.9, 129.8, 128.7, 128.5, 128.4, 128.12, 128.1,127.9, 127.96, 127.9, 127.7, 118.3, 114.5, 98.8, 97.5, 80.7, 77.8, 75.2,75.1, 72.3, 70.4, 68.2, 65.8, 65.1, 63.8, 62.8, 55.7, 40.5, 20.7.

General Procedure B (GPB): Anomeric Deprotection. Ammonium cerium (IV)nitrate (2 eq) is added to a solution of the starting p-methoxyphenylglycoside (1 eq) in acetonitrile/water 7:1 (12.5 mL per mmol). Themixture is stirred at room temperature until TLC (hexanes/ethyl acetate1:1) indicates complete consumption of the starting material, 0.5 to 3d. The reaction mixture is diluted with ethyl acetate, washed with water(twice), saturated aq. sodium chloride, dried over magnesium sulfate andconcentrated. The residue is purified by flash chromatography to givethe product as a foam.

Synthesis of 18

Compound 18 is prepared from compound 13 following general procedure B:4.37 g, 90% (2 anomers), R_(f)=0.2/0.25 (Toluene/EtOAc 5:1); ¹³C-NMR(125 MHz, CDCl₃) δ 170.5, 166.7, 165.7, 164.8, 161.0, 160.5, 154.1,143.2, 143.0, 141.3, 137.8, 137.3, 137.2, 137.1, 133.8, 133.5, 129.9,129.8, 129.4, 129.0, 128.6, 128.4, 128.3, 128.0, 127.9, 127.7, 127.3,127.2, 125.1, 124.9, 120.1, 98.1, 97.9, 95.6, 90.2, 82.4, 79.4, 77.5,76.4, 75.2, 74.8, 74.7. 74.3, 72.5, 70.4, 68.8, 68.7, 68.1, 64.9, 64.7,62.7, 62.6, 61.9, 46.7, 40.7, 20.7

Synthesis of 19

Compound 19 is prepared from compound 14 following general procedure B:2.9 g, 72% (2 anomers), R_(f)=0.4/0.5 (Toluene/EtOAc 7:3); ¹³C-NMR (125MHz, CDCl₃) δ 170.5, 167.1, 166.7, 165.7, 137.9, 137.6, 137.3, 133.5,129.9, 129.8, 129.4, 129.0, 128.6, 128.4, 128.3, 128.1, 128.0, 127.8,127.6, 127.3, 98.3, 98.1, 90.2, 80.1, 79.5, 77.9, 76.5, 75.6, 75.2,75.0, 74.8, 74.4, 70.4, 70.3, 68.3, 65.0, 64.8, 63.3, 62.5, 62.4, 40.7,20.8

Synthesis of 20

Compound 20 is prepared from compound 16 following general procedure B:to obtain a mixture of disaccharides as a foam, 6.0 g, 78% yield (2anomers), TLC R_(f)=0.25/0.3 (EtOAc:petroleum ether, 1:2). HRMS (ESI)calcd for C₅₂H₅₀ClN₃O₁₅Na(M+Na)⁺ m/z 1014.2828, found 1014.283. ¹H-NMR(500 MHz, CDCl₃) δ 8.18-8.12 (m, 4 H), 7.77 (d, J=7.5 Hz, 4 H), 7.59 (d,J=7.6 Hz, 2 H), 7.55 (d, J=7.8 Hz, 2 H), 7.44-7.35 (m, 8H), 7.35-7.30(m, 8H), 7.29-7.26 (m, 6H), 7.24 (d, J=3.0 Hz, 4H), 7.17-7.14 (m, 4H),6.99-6.55 (m, 4H), 5.30 (d, J=8.6 Hz, 2H), 5.26 (d, J=5.5 Hz, 2H), 4.91(d, J=11.3 Hz, 1H), 4.88 (d, J=12.1 Hz, 1H), 4.78 (d, J=11.4 Hz, 2H),4.75 (d, J=9.0 Hz, 2H), 4.74-4.72 (m, 1H), 4.71 (dd, J=3.0 Hz, J=6.1 Hz,1H), 4.69 (d, J=9.0 Hz, 2H), 4.56-4.53 (m, 2H), 4.52-4.51 (m, 2H),4.50-4.47 (m, 2H), 4.39-4.35 (m, 2H), 4.34-4.32 (m, 2H), 4.30-4.28 (m,2H), 4.25-4.21 (m, 2H), 4.29-4.20 (m, 2H), 4.19-4.14 (m, 2H), 4.13 (bs,2H), 4.10 (s, 2H), 4.09 (s, 2H), 4.09-4.0 (m, 1H), 3.93 (t, J=4.6 Hz,1H), 3.89 (d, J=3.2 Hz, 2H), 3.84-3.82 (m, 1H), 3.81-3.80 (m, 1H),3.64-3.60 (m, 1H), 3.54-3.52 (m, 1H), 3.49-3.44 (m, 1H), 3.31 (dd, J=3.9Hz, J=13.8 Hz, 1H), 2.04 (s, 3H), 2.03 (s, 3H); ¹³C-NMR (125 MHz, CDCl₃)δ 170.6, 170.5, 167.1, 167.0, 165.8, 165.7, 154.2, 143.2, 143.1, 141.4,141.3, 137.0, 136.3, 133.6, 133.5, 129.9, 129.8, 129.7, 129.6, 128.9,128.8, 128.7, 128.6, 128.4, 128.3, 128.2, 127.9, 127.8, 127.7, 127.3,125.0, 124.8, 120.1, 114.7, 99.8, 99.6, 93.2, 92.1, 79.7, 78.3, 78.2,76.8, 76.1, 75.8, 74.9, 74.8, 74.4, 73.6, 73.2, 73.1, 72.5, 72.2, 70.2,69.3, 69.1, 69.0, 67.6, 65.2, 65.1, 64.3, 63.3, 63.2, 61.9, 60.4, 46.8,40.7, 20.7.

Synthesis of 21

Compound 21 is prepared from compound 17 following general procedure B:to obtain a mixture of anomers as a syrup 4.1 g, 80% yield (2 anomers),R_(f)=0.2/0.25 (EtOAc:petroleum ether, 1:2). HRMS (ESI) calcd forC₄₄H₄₆ClN₃O₁₃Na(M+Na)⁺ m/z 882.2617, found 882.2619. ¹H-NMR (500 MHz,CDCl₃) δ 8.16-8.11 (m, 4 H), 7.39-7.36 (m, 8 H), 7.35-7.31 (m, 8 H),7.29-7.26 (m, 6 H), 7.25 (d, J=3.8 Hz, 10 H), 7.23-7.20 (m, 2H),7.12-7.09 (m, 2H), 5.28 (d, J=9.6 Hz, 2H), 5.24 (dd, J=7.8 Hz, J=12.3Hz, 2H), 5.08-5.05 (m, 4H), 4.90 (bs, 2H), 4.88 (d, J=3.4 Hz, 1H), 4.85(bs, 1H), 4.78 (d, J=11.8 Hz, 2H), 4.75 (d, J=11.5 Hz, 2H), 4.71 (d,J=10.8 Hz, 2H), 4.54-4.51 (m, 2H), 4.50-4.46 (m, 4H), 4.40-4.36 (m, 2H),4.32-4.27 (m, 2H), 4.24-4.21 (m, 2H), 4.20-4.16 (m, 2H), 4.12 (bs, 1H),4.105 (s, 2H), 4.101 (s, 2H), 3.93-3.87 (m, 2H), 3.62-3.61 (m, 1H), 3.54(t, J=5.3 Hz, 1H), 3.50 (d, J=9.6 Hz, 1H), 3.47 (d, J=7.3 Hz, 1H), 3.41(d, J=10.8 Hz, 1H), 3.36 (t, J=9.5 Hz, 1H), 3.28-3.24 (m, 1H), 2.04 (s,3H), 2.02 (s, 3H); ¹³C-NMR (125 MHz, CDCl₃) δ 170.6, 167.1, 167.0,165.9, 165.8, 137.4, 137.3, 137.1, 136.3, 133.4, 133.3, 129.84, 129.8,128.8, 128.7, 128.6, 128.5, 128.4, 128.3, 128.1, 127.9, 99.6, 99.5,93.1, 92.0, 80.7, 80.6, 76.8, 75.6, 75.3, 75.2, 74.9, 73.6, 73.1, 72.3,72.2, 70.5, 69.4, 67.8, 65.4, 65.2, 64.5, 63.8, 62.7, 60.4, 40.7, 20.7.

General Procedure C (GPC): Trichloroacetimidate Formation. Hemi-acetalstarting material (1 eq) is dissolved in trichloroacetonitrile (20 eq)and the same volume of dichloromethane. The mixture is cooled in anice-bath and sodium hydride (60% in mineral oil) (0.05 eq) is added.After 5 min the ice-bath is removed and the reaction allowed to warm upto room temperature and left until completion. The reaction mixture issubjected to flash chromatography to yield the trichloroacetimidatedonor as an off-white foam.

Synthesis of 22

Compound 22 is prepared from compound 18 following general procedure C:3.8 g, 81% (2 anomers), R_(f)=0.6/0.7 (Toluene/EtOAc 5:1). ¹³C-NMR (125MHz, CDCl₃) δ 170.5, 170.4, 167.0, 165.3, 164.8, 161.0, 160.5, 154.2,154.1, 143.2, 143.0, 141.3, 137.4, 137.1, 133.6, 129.8, 129.7, 129.2,129.1, 129.0, 128.7, 128.5, 128.4, 128.3, 128.2, 127.9, 127.8, 127.7,127.3, 127.2, 125.3, 125.1, 124.9, 120.1, 98.4, 98.2, 95.6, 93.2, 80.8,80.1, 79.9, 77.4, 75.1, 75.0, 74.8, 74.6, 73.7, 72.9, 72.8, 68.9, 68.8,64.8, 64.4, 62.7, 62.5, 61.9, 61.8, 46.7, 40.7, 40.6, 20.7

Synthesis of 23

Compound 23 is prepared from compound 19 following general procedure C:2.84 g, 85% (2 anomers), R_(f)=0.45/0.5 (Toluene/EtOAc 9:1); ¹³C-NMR(125 MHz, CDCl₃) δ 170.5, 170.4, 167.0, 165.3, 164.8, 137.6, 137.2,133.6, 133.5, 129.8, 129.7, 129.3, 129.1, 129.0, 128.6, 128.5, 128.4,128.25, 128.2, 128.15, 128.1, 128.0, 127.8, 127.7, 127.4, 125.3, 98.7,98.3, 95.7, 93.2, 81.4, 80.1, 79.9, 77.9, 77.8, 75.6, 75.5, 75.2, 75.0,74.6, 74.5, 73.8, 73.0, 72.9, 64.8, 64.4, 63.3, 63.1, 62.6, 62.4, 40.7,40.6, 20.8

Synthesis of 24

Compound 24 is prepared from compound 20 following general procedure C:to obtain a mixture of anomers as a, foam 6.1 g, 82% yield (2 anomers),R_(f)=0.35/0.4 (EtOAc:petroleum ether, 1:2). HRMS (ESI) calcd forC₅₄H₅₀Cl₄N₄O₁₅Na(M+Na)⁺ m/z 1157.1924, found 1157.1929. ¹H-NMR (500 MHz,CDCl₃) δ 8.70 (s, 1H), 8.59 (s, 1H), 8.18-8.15 (m, 2 H), 8.07 (dd, J=7.4Hz, J=9.6 Hz, 2 H), 7.78-7.75 (m, 2 H), 7.61-7.58 (m, 2 H), 7.61-7.58(m, 4 H), 7.57-7.54 (m, 4 H), 7.49-7.46 (m, 2 H), 7.44-7.38 (m, 4 H),7.37-7.34 (m, 4 H), 7.32-7.31 (m, 2 H), 7.31-7.27 (m, 2 H), 7.27-7.26(m, 2 H), 7.25 (s, 4 H), 7.20-7.15 (m, 4H), 7.12 (dd, J=4.4 Hz, J=10.0Hz, 2H), 7.0 (dd, J=6.4 Hz, J=9.2 Hz, 2H), 6.50 (d, J=2.7 Hz, 1H), 6.45(s, 1H), 5.41-5.39 (m, 1 H), 5.36 (t, J=2.1 Hz, 1H), 5.02 (d, J=2.9 Hz,1H), 4.97 (d, J=11.4 Hz, 1H), 4.89 (s, 2H), 4.87 (d, J=8.3 Hz, 1H), 4.83(d, J=9.8 Hz, 1H), 4.80 (d, J=9.8 Hz, 2H), 4.78-4.72 (m, 1H), 4.69 (d,J=3.4 Hz, 1H), 4.68-4.64 (m, 2H), 4.63 (d, J=5.3 Hz, 2H), 4.60 (d, J=7.6Hz, 2H), 4.58 (d, J=6.0 Hz, 2H), 4.55 (d, J=4.3 Hz, 2H), 4.53 (d, J=3.2Hz, 2H), 4.52 (d, J=3.7 Hz, 2H), 4.50 (d, J=2.5 Hz, 2H), 4.48 (d, J=3.9Hz, 2H), 4.46-4.42 (m, 1H), 4.39-4.35 (m, 1H), 4.32 (d, J=3.4 Hz, 1H),4.31-4.28 (m, 1H), 4.25-4.22 (m, 1H), 4.22-4.20 (m, 1H), 4.19-4.16 (m,1H), 4.14-4.07 (m, 1H), 4.058 (s, 2H), 4.054 (s, 2H), 3.99 (d, J=10.8Hz, 1H), 3.92 (d, J=10.8 Hz, 1H), 3.76-3.71 (m, 1H), 3.60 (t, J=9.8 Hz,1H), 3.40 (t, J=5.3 Hz, 1H), 3.37 (dd, J=6.8 Hz, J=13.9 Hz, 1H), 2.05(s, 3H), 2.04 (s, 3H); ¹³C-NMR (CDCl₃) δ 171.1, 170.5, 167.0, 166.9,165.7, 165.4, 160.6, 160.5, 154.2, 143.2, 143.1, 141.3, 137.3, 137.2,137.0, 133.6, 133.5, 129.9, 129.8, 129.5, 129.4, 128.8, 128.6, 128.5,128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.3, 125.0,124.9, 124.8, 120.1, 99.5, 99.3, 95.5, 94.9, 78.3, 77.9, 76.8, 75.6,75.4, 75.1, 74.9, 74.6, 74.5, 73.5, 72.4, 71.6, 70.4, 70.2, 69.9, 69.0,68.8, 67.0, 66.4, 65.4, 64.9, 63.3, 63.1, 62.1, 62.0, 60.4, 46.8, 40.6,40.5, 20.7.

Synthesis of 25

Compound 25 is prepared from compound 21 following general procedure C:to obtain a mixture of anomers as a foam, 4.4 g, 94% yield (2 anomers),TLC, R_(f)=0.45/0.5, (EtOAc:petroleum ether, 1:2). HRMS (ESI) calcd forC₄₆H₄₆Cl₄N₄O₁₃Na(M+Na)⁺ m/z 1025.1713, found 1025.1718. ¹H-NMR (500 MHz,CDCl₃) δ 8.68 (s, 1H), 8.57 (s, 1H), 8.16 (dd, J=7.3 Hz, J=9.5 Hz, 2 H),8.05 (dd, J=7.1 Hz, J=9.4 Hz, 2 H), 7.49-7.44 (m, 2 H), 7.42-7.38 (m, 4H), 7.37-7.30 (m, 10 H), 7.29-7.23 (m, 12 H), 7.14-7.12 (m, 6 H), 6.50(d, J=2.8 Hz, 1H), 6.43 (s, 1H), 5.38 (dd, J=4.5 Hz, J=10.2 Hz, 1 H),5.35-5.33 (m, 1H), 5.28 (s, 1H), 5.04 (d, J=3.4 Hz, 1H), 4.96 (d, J=11.5Hz, 1H), 4.87 (s, 1H), 4.80 (d, J=10.2 Hz, 1H), 4.76 (t, J=10.2 Hz, 1H),4.68 (d, J=3.4 Hz, 1H), 4.66-4.63 (m, 1H), 4.62 (d, J=6.2 Hz, 1H),4.60-4.56 (m, 1H), 4.54-53 (m, 1H), 4.52-4.49 (m, 2H), 4.50-4.44 (m,1H), 4.43 (d, J=5.9 Hz, 2H), 4.40 (d, J=4.2 Hz, 2H), 4.38 (t, J=2.5 Hz,1H), 4.36 (d, J=7.0 Hz, 2H), 4.32 (t, J=2.5 Hz, 1H), 4.30-4.28 (m, 1H),4.27 (d, J=10.8 Hz, 1H), 4.23-4.17 (m, 1H), 4.15-4.13 (m, 1H), 4.12 (s,2H), 4.11 (s, 2H), 4.06 (s, 1H), 4.04 (d, J=2.4 Hz, 1H), 4.04-4.02 (m,1H), 4.0-3.97 (m, 1H), 3.96-3.93 (m, 1H), 3.73 (t, J=9.8 Hz, 1H), 3.61(d, J=9.8 Hz, 1 H), 3.59 (d, J=9.8 Hz, 1 H), 3.46-3.41 (m, 1H),3.40-3.36 (m, 1H), 3.35 (d, J=3.8 Hz, 1H), 3.33 (dd, J=3.3 Hz, J=6.1 Hz,1H), 2.03 (s, 6H); ¹³C-NMR (125 MHz, CDCl₃) δ 171.1, 170.6, 167.0,166.9, 165.7, 165.5, 163.4, 160.6, 160.5, 137.5, 137.4, 137.3, 137.2,133.4, 129.9, 129.8, 129.6, 129.3, 128.7, 128.6, 128.5, 128.4, 128.1,128.0, 127.9, 99.4, 99.2, 95.5, 94.9, 80.7, 80.4, 77.8, 77.0, 76.8,75.4, 75.3, 75.2, 75.0, 74.6, 74.5, 73.6, 72.3, 71.5, 70.6, 70.3, 67.2,66.5, 65.7, 65.0, 63.9, 63.6, 62.7, 60.4, 40.7, 40.6, 21.0, 20.8.

General Procedure D (GPD): Fmoc Deprotection. The appropriate Fmocderivative is dissolved in a mixture of dichloromethane andtriethylamine 4:1 (v/v, 20 mL per mmol) and left at ambient temperatureuntil completion, usually 3 to 5 h. Subsequently the mixture is dilutedwith dichloromethane, washed with diluted aq. HCl, water and saturatedaq. sodium chloride, dried over magnesium sulfate and concentrated. Theresidue is purified by flash chromatography to afford the desiredalcohols as foams.

General Procedure E (GPE): Chain Extension Glycosylation. A solution ofthe trichloroacetimidate donor (1.3 eq) and the glycosyl acceptoralcohol (1 eq) in anhydrous toluene (40 mL per mmol acceptor) is cooledto reaction temperature (between −10 and −20° C.), powdered molecularsieves (4 Å) are added and the suspension stirred at the temperature.After 15 min, trimethylsilyl trifluoromethanesulfonate (0.3 eq) is addedand the reaction mixture stirred at reaction temperature until TLC(toluene/ethyl acetate 4:1) indicated completion. The mixture is dilutedwith ethyl acetate and filtered through celite into aq. sodiumbicarbonate, the organic layer is washed with water and saturated aq.sodium chloride, dried over magnesium sulfate and concentrated. Theresidue is purified by flash chromatography to yield the fully protectedoligosaccharides.

Synthesis of 26

Compound 26 is prepared from compound 16 following general procedure D:2.55 g, 88% yield, TLC, R_(f)=0.2 (EtOAc:petroleum ether, 1:2). HRMS(ESI) calcd for C₄₄H₄₆ClN₃O₁₄Na(M+Na)⁺ m/z 898.2566, found 898.2555.¹H-NMR (500 MHz, CDCl₃) δ 8.18 (dd, J=7.1 Hz, J=9.4 Hz, 2 H), 7.52-7.48(m, 3 H), 7.47-7.43 (m, 3 H), 7.38-7.35 (m, 2 H), 7.34-7.27 (m, 3 H),7.24-7.13 (m, 2 H), 7.06 (d, J=9.5 Hz, 2 H), 6.85 (d, J=9.5 Hz, 2 H),5.62 (s, 1H), 5.36 (s, 1H), 5.02 (d, J=10.3 Hz, 1H), 4.81 (d, J=10.8 Hz,1H), 4.67 (d, J=3.6 Hz, 1H), 4.61-4.58 (m, 1H), 4.53 (d, J=9.1 Hz, 1H),4.51 (dd, J=6.7 Hz, J=10.3 Hz, 1H), 4.49 (d, J=4.3 Hz, 1H), 4.39 (d,J=10.6 Hz, 1H), 4.33 (d, J=3.5 Hz, 1H), 4.33 (d, J=4.4 Hz, 1H),4.22-4.20 (m, 1H), 4.17 (d, J=2.2 Hz, 1H), 3.87 (d, J=2.0 Hz, 2H), 3.78(s, 3H), 3.73 (t, J=2.8 Hz, 1H), 3.50 (d, J=8.2 Hz, 1H), 3.37 (d, J=8.9Hz, 1H), 3.36-3.31 (m, 1H), 3.26 (dd, J=6.1 Hz, J=13.6 Hz, 1H), 2.05 (s,3H); ¹³C-NMR (CDCl₃) δ 171.8, 166.9, 165.7, 155.3, 150.2, 137.7, 137.6,133.4, 129.9, 129.8, 129.0, 128.7, 128.6, 128.4, 128.2, 128.13, 128.1,128.0, 125.3, 118.3, 114.6, 98.9, 97.6, 80.1, 75.2, 75.0, 72.4, 72.36,72.35, 70.5, 68.3, 65.8, 65.1, 63.3, 62.9, 55.7, 40.5, 20.7.

Synthesis of 27

Compound 27 is prepared from compound 13 following general procedure D:4.36 g, 91%, R_(f)=0.3 (Toluene/EtOAc 4:1). ¹³C-NMR (125 MHz, CDCl₃) δ171.9, 167.0, 165.1, 155.7, 151.0, 137.8, 137.3, 133.5, 129.8, 129.5,128.7, 128.6, 128.4, 128.2, 127.8, 127.7, 118.7, 114.5, 100.1, 98.2,82.8, 79.2, 75.4, 74.5, 74.2, 73.6, 72.5, 71.4, 70.7, 64.9, 62.9, 62.7,55.6, 40.6, 20.8

Synthesis of 28

Compound 28 is prepared from compound 26 and compound 24 followinggeneral procedure E: 450 mg, 95% yield (beta), TLC, R_(f)=0.35(EtOAc:petroleum ether, 1:2). HRMS (ESI) calcd forC₉₆H₉₄Cl₂N₆O₂₈Na(M+Na)⁺ m/z 1871.5391, found 1871.5383. ¹H-NMR (500 MHz,CDCl₃) δ 8.17 (dd, J=6.8 Hz, J=9.4 Hz, 2 H), 8.11 (dd, J=6.8 Hz, J=9.8Hz, 2 H), 7.77 (d, J=7.4 Hz, 2H), 7.60 (d, J=7.4 Hz, 2H), 7.55 (d, J=7.5Hz, 1H), 7.47-7.43 (m, 4H), 7.43-7.39 (m, 3H), 7.39-7.36 (m, 3H),7.35-7.32 (m, 4H), 7.32-7.31 (m, 4H), 7.30-7.23 (m, 4H), 7.20-7.15 (m,4H), 7.08-7.05 (m, 4H), 7.06 (d, J=9.5 Hz, 2H), 6.85 (d, J=8.9 Hz, 2H),5.64 (bd, 1H), 5.35 (t, J=2.4 Hz, 1H), 5.15 (t, J=3.9 Hz, 1H), 5.12 (d,J=3.5 Hz, 1H), 5.02 (d, J=11.8 Hz, 1H), 4.87 (d, J=11.5 Hz, 1H), 4.81(d, J=11.3 Hz, 1H), 4.76 (d, J=2.5 Hz, 1H), 4.73 (t, J=4.6 Hz, 1H), 4.65(d, J=3.7 Hz, 1H), 4.59-4.55 (m, 1H), 4.51-4.48 (m, 2H), 4.48-4.44 (m,2H), 4.38-4.34 (m, 3H), 4.33-4.29 (m, 4H), 4.28-4.25 (m, 2H), 4.24-4.23(m, 1H), 4.22-4.20 (m, 2H), 4.19-4.15 (m, 2H), 4.09-4.07 (m, 2H),4.05-4.03 (m, 1H), 4.03-4.01 (m, 1H), 4.0 (d, J=10.2 Hz, 1H), 3.96-3.94(m, 1H), 3.92 (d, J=3.0 Hz, 2H), 3.83 (d, J=3.6, 2H), 3.77 (s, 3H),3.72-3.68 (m, 1H), 3.68-3.65 (m, 1H), 3.60 (t, J=9.8, 1H), 3.38-3.28 (m,1H), 2.03 (s, 3H), 2.02 (s, 3H); ¹³C NMR (CDCl₃) δ 171.1, 170.5, 170.4,166.8, 166.7, 165.7, 165.4, 155.2, 154.2, 150.1, 143.2, 143.0, 141.35,141.3, 137.7, 137.6, 137.2, 137.1, 133.5, 133.4, 129.9, 129.7, 129.5,128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8,127.7, 127.3, 125.0, 124.8, 120.1, 118.3, 114.6, 98.8, 98.1, 97.8, 97.6,79.1, 77.9, 75.2, 75.1, 74.99, 74.9, 74.5, 74.4, 73.9, 73.4, 73.2, 72.4,72.1, 70.3, 69.9, 68.8, 68.3, 67.2, 65.8, 64.9, 63.9, 63.7, 64.9, 63.9,63.7, 63.1, 62.3, 61.9, 60.4, 55.7, 46.7, 40.6, 40.5, 20.7.

Synthesis of 29

Compound 29 is prepared from compound 27 and compound 22 followinggeneral procedure E: 8.0 g, 87% (beta), R_(f)=0.45 (toluene/EtOAc 4:1).¹³C-NMR (125 MHz, CDCl₃) δ 170.5, 170.4, 169.9, 166.4, 165.1, 164.9,155.7, 154.1, 150.9, 143.2, 153.0, 141.0, 138.3, 137.3, 137.2, 137.1,133.8, 135.5, 129.8, 129.5, 129.0, 128.9, 128.8, 128.6, 128.4, 128.35,128.3, 128.2, 128.0, 127.9, 127.7, 127.7, 127.5, 127.4, 127.2, 125.3,125.1, 124.9, 120.1, 118.8, 114.5, 101.0, 100.1, 97.9, 97.7, 82.7, 77.9,77.7, 77.4, 75.4, 75.2, 75.1, 74.7, 74.6, 74.5, 74.3, 74.1, 73.6, 72.4,70.4, 69.8, 68.8, 64.9, 64.7, 64.2, 62.7, 62.6, 62.0, 61.8, 55.6, 46.7,40.7, 40.4, 20.75, 20.7

Synthesis of 30

Compound 30 is prepared from compound 28 following general procedure D:388 mg, 84% yield, TLC R_(f)=0.45 (EtOAc:petroleum ether, 1:1). HRMS(ESI) calcd for C₈₁H₈₄Cl₂N₆O₂₆Na(M+Na)⁺ m/z 1649.471, found 1649.4702.¹H-NMR (500 MHz, CDCl₃) δ 8.16 (dd, J=6.5 Hz, J=9.0 Hz, 2 H), 8.11 (dd,J=7.1 Hz, J=9.2 Hz, 2 H), 7.52-7.48 (m, 4 H), 7.46-7.39 (m, 4 H),7.38-7.34 (m, 8 H), 7.33-7.29 (m, 4 H), 7.28-7.23 (m, 4 H), 7.18-7.16(m, 2 H), 7.05 (d, J=9.2 Hz, 2 H), 6.85 (d, J=9.2 Hz, 2 H), 5.62 (s,1H), 5.34 (s, 1H), 5.15 (t, J=4.3 Hz, 1H), 5.0 (d, J=11.9 Hz, 1H), 4.86(d, J=11.5 Hz, 1H), 4.80 (d, J=11.8 Hz, 1H), 4.77-4.76 (m, 2H), 4.53 (d,J=8.0 Hz, 1H), 4.50 (d, J=7.6 Hz, 1H), 4.47 (d, J=5.7 Hz, 1H), 4.59 (bs,1H), 4.58-4.54 (m, 1H), 4.53 (d, J=7.6 Hz, 1H), 4.50 (d, J=8.3 Hz, 1H),4.47 (d, J=6.0 Hz, 1H), 4.45-4.42 (m, 1H), 4.40-4.39 (m, 1H), 4.35-4.30(m, 1H), 4.29 (d, J=4.5 Hz, 1H), 4.27-4.24 (m, 1H), 4.23-4.22 (m, 1H),4.19-4.16 (m, 1H), 4.15 (d, J=2.6 Hz, 1H), 4.12 (d, J=9.8 Hz, 1H), 4.08(s, 1H), 4.05 (d, J=4.3 Hz, 1H), 4.03 (d, J=4.5 Hz, 1H), 3.97 (d, J=10.3Hz, 2H), 3.90 (d, J=2.1 Hz, 2H), 3.81 (d, J=3.5 Hz, 2H), 3.76 (s, 3H),3.74-3.70 (m, 1H), 3.70-3.67 (m, 1H), 3.60 (d, J=10.5 Hz, 1H), 3.56 (d,J=9.7 Hz, 1H), 3.41-3.36 (m, 1H), 3.31 (dd, J=5.7 Hz, J=13.5 Hz, 1H),3.23 (dd, J=6.8 Hz, J=13.7 Hz, 1H), 3.06 (d, J=4.5 Hz, 1H), 2.02 (s,3H), 2.01 (s, 3H); ¹³C-NMR (125 MHz, CDCl₃) δ 171.6, 171.1, 170.7,167.0, 166.8, 165.7, 165.5, 155.2, 150.1, 137.7, 137.6, 137.3, 133.5,133.4, 129.9, 129.8, 129.5, 128.7, 128.6, 128.5, 128.4, 128.3, 128,1,127.7, 118.3, 114.6, 98.9, 98.3, 97.8, 97.5, 79.7, 78.9, 76.9, 75.5,75.2, 74.9, 74.6, 74.4, 73.4, 72.4, 72.1, 71.3, 70.6, 70.3, 68.3, 67.9,65.7, 64.9, 63.8, 63.6, 63.1, 62,8, 62.4, 60.4, 55.6, 40.5, 20.7.

Synthesis of 31

Compound 31 is prepared from compound 29 following general procedure D:600 mg, 85%, R_(f)=0.2 (Toluene/EtOAc 7:3). ¹³C-NMR (125 MHz, CDCl₃) δ171.9, 170.5, 166.9, 166.4, 165.1, 164.9, 155.7, 150.9, 138.3, 137.8,137.3, 137.2, 133.8, 133.5, 129.8, 129.5, 128.9, 128.8, 128.7, 128.6,128.4, 128.3, 128.2, 128.1, 127.7, 127.5, 127.3, 127.0, 125.3, 118.8,114.5, 101.0, 100.0, 98.3, 97.7, 82.8, 82.7, 79.2, 77.9, 77.7, 75.4,75.0, 74.7, 74.6, 74.3, 73.6, 72.5, 71.4, 70.6, 69.8, 64.9, 64.2, 62.7,62.0, 55.6, 40.4, 20.7

Synthesis of 32

Compound 32 is prepared from compound 30 and compound 24 followinggeneral procedure E: 1.51 g, 86% yield (beta), R_(f)=0.21(EtOAc:petroleum ether, 1:2). HRMS (ESI) calcd forC₁₃₃H₁₃₂Cl₃N₉O₄₀Na(M+Na)⁺ m/z 2622.7535, found 2622.7549. ¹H-NMR (500MHz, CDCl₃) δ 8.17 (dd, J=6.5 Hz, J=8.9 Hz, 2 H), 8.12-8.08 (m, 4 H),7.76-7.73 (m, 2H), 7.59 (d, J=7.3 Hz, 2H), 7.54 (d, J=7.7 Hz, 8H),7.50-7.43 (m, 6H), 7.42-7.35 (m, 12H), 7.34-7.29 (m, 8H), 7.28-7.19 (m,6H), 7.18-7.13 (m, 4H), 7.08-7.04 (m, 2H), 7.05 (d, J=9.1 Hz, 2H), 6.85(d, J=8.7 Hz, 2H), 5.63 (d, J=4.6 Hz, 1H), 5.35 (t, J=3.6 Hz, 1H),5.17-5.12 (m, 1H), 5.10 (d, J=4.6 Hz, 1H), 5.01 (d, J=11.9 Hz, 1H), 4.87(d, J=7.7 Hz, 1H), 4.84 (d, J=7.7 Hz, 1H), 4.81-4.79 (m, 2H), 4.78-4.75(m, 3H), 4.74 (d, J=5.9 Hz, 1H), 4.71 (bs, 1H), 4.70 (d, J=3.8 Hz, 1H),4.63 (d, J=4.0 Hz, 1H), 4.59-4.54 (m, 4H), 4.54-4.49 (m, 4H), 4.48-4.42(m, 3H), 4.41-4.37 (m, 4H), 4.35-4.29 (m, 4H), 4.28-4.25 (m, 3H),4.24-4.22 (m, 2H), 4.21-4.17 (m, 2H), 4.16-4.14 (m, 2H), 4.08-4.04 (m,2H), 4.03-4.01 (m, 1H), 3.97 (d, J=10.2 Hz, 1H), 3.90 (s, 2H), 3.89 (s,2H), 3.81 (d, J=4.0 Hz, 2H), 3.75 (s, 3H), 3.74-3.71 (m, 1H), 3.71-3.67(m, 1H), 3.67-3.64 (m, 1H), 3.64-3.60 (m, 1H), 3.58 (t, J=9.5, 1H), 3.32(d, J=4.3, 1H), 3.30-3.28 (m, 1H), 3.28 (d, J=3.9, 1H), 2.03 (s, 3H),2.0 (s, 3H), 2.0 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ 171.6, 171.1,170.5, 170.4, 166.9, 166.8, 166.7, 165.7, 165.5, 165.4, 163.2, 155.2,154.2, 150.2, 143.2, 143.1, 141.4, 137.7, 137.6, 137.3, 137.2, 137.1,136.5, 134.1, 133.6, 133.4, 129.9, 129.8, 129.5, 129.4, 128.8, 128.7,128.6, 128.5, 128.4, 128.35, 128.3, 128.25, 128.2, 128.1, 128.0, 127.9,127.8, 127.3, 125.0, 124.8, 120.2, 118.3, 114.6, 98.8, 98.3, 98.1, 97.9,97.8, 97.5, 80.1, 79.0, 78.9, 78.3, 77.9, 76.9, 76.2, 75.8, 75.4, 75.1,74.9, 74.7, 74.6, 74.5, 74.1, 74.0, 73.8, 73.5, 73.3, 73.2, 72.4, 72.1,71.4, 70.7, 70.4, 70.3, 70.2, 69.8, 69.5, 68.9, 68.8, 68.3, 67.9, 67.6,67.1, 65.9, 65.7, 65.2, 64.9, 64.4, 63.9, 63.8, 63.7, 63.6, 63.3, 63.1,62.3, 62.2, 61.9, 60.4, 55.7, 46.8, 40.7, 40.5, 22.7

Synthesis of 33

Compound 33 is prepared from compound 30 and compound 25 followinggeneral procedure E: The residue is purified by silica gelchromatography (EtOAc:petroleum ether, 1:2) to furnish the disaccharideas a foam, 375 mg, 74% yield, TLC, R_(f)=0.15 (EtOAc:petroleum ether,1:2) HRMS (ESI) calcd for C₁₂₅H₁₂₈Cl₃N₉O₃₈Na(M+Na)⁺ m/z 2490.7324, found2490.7297. ¹H-NMR (500 MHz, CDCl₃) δ 8.15 (dd, J=6.7 Hz, J=9.6 Hz, 2 H),8.09 (d, J=8.1 Hz, 4 H), 7.50-7.40 (m, 4 H), 7.39-7.34 (m, 6 H),7.33-7.28 (m, 6H), 7.27-7.20 (m, 10H), 7.20-7.16 (m, 10H), 7.14-7.11 (m,8H), 7.05 (d, J=8.9 Hz, 2H), 6.85 (d, J=9.5 Hz, 2H), 5.62 (d, J=4.0 Hz,1H), 5.35 (d, J=3.7 Hz, 1H), 5.14 (dd, J=5.2 Hz, J=13.1 Hz, 1H), 5.10(d, J=3.6 Hz, 1H), 5.07 (d, J=3.7 Hz, 1H), 5.01 (d, J=11.5 Hz, 1H), 4.84(d, J=4.4 Hz, 2H), 4.82 (t, J=4.3 Hz, 2H), 4.77-4.73 (m, 2H), 4.72 (d,J=3.6 Hz, 2H), 4.71 (d, J=3.7 Hz, 2H), 4.63 (d, J=3.8 Hz, 2H), 4.57-4.53(m, 2H), 4.53-4.48 (m, 3H), 4.47-4.45 (m, 2H), 4.45-4.43 (m, 2H),4.42-4.39 (m, 2H), 4.35-4.30 (m, 2H), 4.29 (d, J=3.7 Hz, 2H), 4.26 (d,J=4.3 Hz, 1H), 4.24-4.18 (m, 1H), 4.18-4.15 (m, 1H), 4.10 (d, J=2.2 Hz,2H), 4.08-4.05 (m, 2H), 4.04-4.01 (m, 2H), 4.0 (d, J=4.6 Hz, 2H), 3.90(d, J=10.3 Hz, 2H), 3.92-3.89 (m, 1H), 3.88-3.87 (m, 4H), 3.81 (d, J=4.8Hz, 2H), 3.77 (s, 3H), 3.73 (d, J=8.8 Hz, 1H), 3.70-3.64 (m, 1H), 3.62(d, J=10.6 Hz, 1H), 3.58 (d, J=10.6 Hz, 1H), 3.54 (d, J=8.8 Hz, 1H),3.43 (t, J=9.3 Hz, 1H), 3.30 (d, J=3.9 Hz, 1H), 3.28-3.25 (m, 1H),3.25-3.23 (m, 1H), 2.013 (s, 3H), 1.99 (s, 3H), 1.97 (s, 3H); ¹³C NMR(CDCl₃) δ 171.1, 170.5, 170.4, 166.8, 166.7, 165.7, 165.5, 165.4, 164.9,155.2, 143.2, 143.1, 143.0, 141.3, 137.7, 137.6, 137.3, 137.0, 133.6,133.4, 129.8, 129.7, 129.5, 129.4, 128.9, 128.8, 128.6, 128.5, 128.4,128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5, 127.2,125.0, 124.8, 120.1, 118.2, 114.5, 99.6, 98.8, 98.3, 98.0, 97.9, 97.8,78.9, 78.8, 77.9, 77.3, 77.0, 76.8, 75.8, 75.3, 75.1, 75.0, 74.9, 74.6,74.5, 74.4, 74.2, 74.0, 73.8, 73.6, 73.5, 73.4, 73.3, 72.3, 72.2, 72.1,70.4, 70.3, 70.2, 69.8, 69.1, 68.8, 68.2, 65.7, 65.2, 65.0, 64.9, 64.3,63.8, 63.7, 63.6, 63.3, 63.1, 62.3, 62.2, 61.9, 60.4, 55.7, 46.8, 40.7,40.5, 40.3, 20.7.

Synthesis of 34

Compound 34 is prepared from compound 31 and compound 22 followinggeneral procedure E: 5.25 g, 94% (beta), R_(f)=0.45 (Toluene/EtOAc 4:1).¹³C-NMR (125 MHz, CDCl₃) δ 170.4, 169.9, 166.4, 165.9, 165.1, 165.0,164.9, 155.7, 154.1, 151.0, 143.2, 143.0, 141.3, 138.3, 137.3, 137.2,137.1, 133.8, 133.5, 129.8, 129.7, 129.5, 129.0, 128.9, 128.6, 128.4,128.35, 128.3, 128.2, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5, 127.45,127.4, 127.3, 125.1, 124.9, 120.1, 118.8, 114.5, 100.9, 100.8, 100.1,97.8, 97.7, 82.8, 82.7, 77.7, 77.6, 77.5, 74.5, 75.3, 75.2, 75.1, 74.9,74.7, 74.6, 74.3, 74.2, 74.1, 73.6, 72.4, 72.3, 70.4, 69.8, 68.8, 64.9,64.2, 62.7, 62.6, 61.9, 61.8, 55.6, 46.7, 40.4, 40.3, 20.75, 20.7

Synthesis of 35

Compound 35 is prepared from compound 31 and compound 23 followinggeneral procedure E: 591 mg, 78% (beta), R_(f)=0.5 (Toluene/EtOAc 4:1).¹³C-NMR (125 MHz, CDCl₃) δ 170.5, 166.9, 166.4, 165.1, 165.0, 164.9,155.7, 150.9, 138.3, 138.2, 137.5, 137.3, 137.3, 137.2, 133.8, 133.7,133.4, 129.8, 129.7, 129.5, 129.1, 129.0, 128.9, 128.8, 128.6, 128.5,128.4, 128.3, 128.1, 128.0, 127.7, 127.6, 127.5, 127.4, 125.3, 118.8,114.5, 100.9, 100.8, 100.0, 98.0, 97.8, 97.7, 82.8, 82.7, 80.1, 77.8,77.7, 77.5, 75.6, 75.5, 75.2, 75.0, 74.9, 74.7, 74.6, 74.3, 74.2, 74.1,73.5, 72.4, 72.3, 70.3, 69.8, 65.0, 64.4, 64.2, 63.2, 62.7, 62.6, 62.4,61.9, 61.8, 55.6, 40.5, 40.4, 40.3, 20.7

Synthesis of 36

Compound 36 is prepared from compound 32 following general procedure D:The residue is purified by silica gel chromatography (EtOAc:petroleumether, 1:1) to furnish the disaccharide as a foam, 550 mg, 88% yield;TLC, R_(f)=0.45 (EtOAc:petroleum ether, 1:1). HRMS (ESI) calcd forC₁₁₈H₁₂₂Cl₃N₉O₃₈Na(M+Na)⁺ m/z 2400.6854, found 2400.6853. ¹H-NMR (500MHz, CDCl₃) δ 8.16-8.07 (m, 6 H), 7.51-7.46 (m, 5 H), 7.46-7.38 (m, 10H), 7.37-7.22 (m, 8H), 7.21-7.18 (m, 10H), 7.16-7.12 (m, 6H), 7.05 (d,J=10.1 Hz, 2H), 6.84 (d, J=9.3 Hz, 2H), 5.62 (bd, 1H), 5.35 (t, J=2.1Hz, 1H), 5.15 (dd, J=3.3 Hz, J=10.0 Hz, 1H), 5.11 (d, J=3.6 Hz, 1H),5.09 (d, J=3.8 Hz, 1H), 5.0 (d, J=11.5 Hz, 1H), 4.86 (d, J=7.0 Hz, 1H),4.83 (d, J=7.5 Hz, 2H), 4.80 (d, J=11.6 Hz, 1H), 4.76-4.73 (m, 2H), 4.72(d, J=10.4 Hz, 1H), 4.63 (d, J=4.1 Hz, 2H), 4.59-4.54 (m, 3H), 4.53-4.51(m, 1H), 4.51 (d, J=3.5 Hz, 2H), 4.49 (d, J=10.3 Hz, 2H), 4.45-4.43 (m,1H), 4.43-4.40 (m, 1H), 4.39-4.38 (m, 2H), 4.37-4.33 (m, 2H), 4.33-4.30(m, 2H), 4.30-4.27 (m, 2H), 4.27-4.20 (m, 2H), 4.19-4.16 (m, 1H), 4.15(d, J=2.8 Hz, 1H), 4.12-4.07 (m, 1H), 4.07-4.04 (m, 1H), 4.04 (d, J=4.0Hz, 1H), 4.02 (d, J=4.5 Hz, 1H), 3.97 (d, J=10.2 Hz, 1H), 3.89-3.87 (m,4H), 3.81 (d, J=4.2 Hz, 2H), 3.75 (s, 3H), 3.64 (d, J=9.8 Hz, 2H), 3.60(d, J=9.1 Hz, 2H), 3.57 (dd, J=4.9 Hz, J=13.3 Hz, 1H), 3.41-3.35 (m,1H), 3.31 (d, J=3.9 Hz, 1H), 3.29 (t, J=3.25 Hz, 1H), 3.27 (d, J=3.9 Hz,1H), 3.23 (d, J=3.9 Hz, 2H), 3.21 (d, J=3.8 Hz, 1H), 3.07 (d, J=4.0 Hz,1H), 2.02 (s, 3H), 2.016 (s, 3H), 2.01 (s, 3H); ¹³C-NMR (125 MHz, CDCl₃)δ 171.6, 171.1, 170.7, 170.6, 167.0, 165.8, 165.7, 165.52, 165.5, 155.2,150.1, 137.8, 137.6, 137.3, 137.2, 133.5, 133.4, 130.9, 129.9, 129.8,129.7, 129.5, 129.4, 128.7, 128.66, 128.6, 128.5, 128.4, 128.3, 128.2,128.1, 128.0, 127.9, 127.7, 127.6, 125.7, 118.3, 114.6, 99.6, 98.9,98.3, 98.2, 97.8, 97.5, 80.1, 79.8, 78.9, 78.7, 76.9, 75.4, 75.2, 74.9,74.6, 74.5, 74.3, 74.2, 73.44, 73.4, 72.3, 72.1, 71.7, 71.3, 70.6, 70.5,70.4, 70.3, 70.2, 68.3, 67.8, 67.6, 65.7, 64.9, 63.9, 63.6, 63.5, 63.3,63.1, 62.9, 62.3, 62.2, 60.4, 55.7, 40.7, 40.51, 20.7.

Synthesis of 37

Compound 37 is prepared from compound 34 following general procedure D:2.62 g, 80%, R_(f)=0.18 (Toluene/EtOAc 7:3). ¹³C-NMR (125 MHz, CDCl₃) δ171.9, 170.5, 166.9, 166.4, 165.1, 165.0, 164.9, 155.7, 150.9, 138.3,138.0, 137.8, 137.3, 137.2, 133.7, 133.5, 129.8, 129.5, 129.0, 128.95,128.9, 128.8, 128.7, 128.6, 128.4, 128.3, 128.2, 128.1, 127.7, 127.5,127.45, 127.3, 127.0, 125.3, 118.8, 114.5, 100.9, 100.8, 100.0, 98.3,97.8, 97.7, 82.8, 82.7, 79.2, 77.7, 77.65, 77.6, 76.55, 75.4, 75.0,74.9, 74.7, 74.6, 74.3, 73.6, 72.5, 72.3, 71.4, 70.6, 69.8, 64.9, 64.4,64.2, 62.7, 61.9, 61.8, 55.6, 40.4, 40.3, 20.7

Synthesis of 38

Compound 38 is prepared from compound 36 and compound 24 followinggeneral procedure E: 272 mg, 80% yield (beta), R_(f)=0.15(EtOAc:petroleum ether, 1:2). HRMS (ESI) calcd forC₁₇₀H₁₇₀Cl₄N₁₂O₅₂Na(M+Na)⁺ m/z 3373.9672, found 3373.9951. ¹H-NMR (500MHz, CDCl₃) δ 8.16 (dd, J=7.0 Hz, J=9.7 Hz, 2 H), 8.12-8.07 (m, 4 H),7.76 (d, J=7.8 Hz, 1H), 7.60 (d, J=7.6 Hz, 1H), 7.55 (d, J=7.6 Hz, 1H),7.51 (bd, 1H), 7.49-7.46 (m, 6H), 7.46-7.43 (m, 8 H), 7.43-7.40 (m, 8H),7.40-7.37 (m, 5H), 7.37-7.35 (m, 4H), 7.35-7.30 (m, 8H), 7.29-7.24 (m,6H), 7.23-7.19 (m, 4H), 7.19-7.16 (m, 4H), 7.15-7.12 (m, 4H), 7.08-7.05(m, 2H), 7.05 (d, J=9.1 Hz, 2H), 6.85 (d, J=9.1 Hz, 2H), 5.63 (d, J=3.7Hz, 1H), 5.35 (t, J=3.6 Hz, 1H), 5.16-5.11 (m, 3H), 5.10 (d, J=4.4 Hz,1H), 5.08 (d, J=4.0 Hz, 1H), 5.01 (d, J=11.8 Hz, 1H), 4.86-4.79 (m, 8H),4.78-4.71 (m, 6H), 4.71 (dd, J=4.7 Hz, J=10.2 Hz, 2H), 4.63 (d, J=3.9Hz, 1H), 4.58-4.53 (m, 6H), 4.53 (d, J=5.5 Hz, 1H), 4.50 (d, J=4.3 Hz,1H), 4.48-4.46 (m, 4H), 4.45-4.40 (m, 6H), 4.39-4.35 (m, 6H), 4.35-4.31(m, 4H), 4.30-4.27 (m, 3H), 4.27-4.23 (m, 2H), 4.23-4.19 (m, 2H),4.19-4.15 (m, 2H), 4.10-4.07 (m, 2H), 4.06-4.0 (m, 1H), 3.97 (d, J=11.4Hz, 1H), 3.90-3.87 (m, 4H), 3.81 (d, J=4.7 Hz, 2H), 3.76 (s, 3H),3.75-3.74 (m, 1H), 3.73-3.65 (m, 1H), 3.64 (q, J=8.1 Hz, 2H), 3.57 (t,J=8.8, 1H), 3.32 (d, J=3.5, 1H), 3.31-3.27 (m, 1H), 3.27 (t, J=3.0, 1H),2.03 (s, 3H), 2.01 (s, 3H), 2.0 (s, 3H), 1.99 (3H); ¹³C NMR (125 MHz,CDCl₃) δ 170.6, 170.5, 170.4, 166.9, 166.8, 166.77, 166.7, 165.6, 165.5,165.4, 155.3, 154.2, 150.2, 143.2, 143.1, 141.4, 137.7, 137.6, 137.3,137.2, 137.16, 137.1, 133.6, 133.5, 129.9, 129.8, 129.5, 129.4, 128.8,128.7, 128.5, 128.4, 128.35, 128.3, 128.27, 128.2, 128.1, 128.0, 127.9,127.8, 127.7, 127.3, 125.1, 124.9, 120.2, 118.3, 114.6, 98.8, 98.3,98.2, 98.1, 98.06, 98.0, 97.9, 97.8, 97.6, 79.0, 78.9, 78.7, 77.9, 76.9,75.4, 75.3, 75.1, 75.0, 74.9, 74.7, 74.6, 74.3, 74.2, 74.0, 73.9, 73.5,73.4, 72.4, 72.1, 70.4, 70.3, 70.2, 69.8, 68.3, 67.7, 67.5, 67.2, 65.7,64.9, 64.7, 63.9, 63.8, 63.77, 63.7, 63.6, 63.58, 63.5, 63.1, 62.3,62.2, 61.9, 55.7, 46.8, 40.7, 40.5, 20.8.

Synthesis of 39

Compound 39 is prepared from compound 36 and compound 25 followinggeneral procedure E: The residue is purified by silica gelchromatography (EtOAc:petroleum ether, 1:2) to furnish the disaccharideas a foam, 260 mg, 82% yield, R_(f)=0.22 (EtOAc:petroleum ether, 2:3).HRMS (ESI) calcd for C₁₆₂H₁₇₀Cl₄N₁₂O₅₀Na(M+Na)⁺ m/z 3245.9781, found3245.9404. ¹H-NMR (500 MHz, CDCl₃) δ 8.15 (dd, J=6.8 Hz, J=9.5 Hz, 2 H),8.10-8.06 (m, 4 H), 7.50-7.46 (m, 4 H), 7.45-7.40 (m, 8 H), 7.40-7.34(m, 8 H), 7.33-7.28 (m, 12H), 7.27-7.22 (m, 10H), 7.21-7.16 (m, 8H),7.14-7.11 (m, 9H), 7.05 (d, J=9.5 Hz, 2H), 6.85 (d, J=8.9 Hz, 2H), 5.62(d, J=3.4 Hz, 1H), 5.34 (t, J=3.7 Hz, 2H), 5.14-5.10 (m, 2H), 5.10 (t,J=3.9 Hz, 2H), 5.07 (d, J=4.1 Hz, 1H), 5.01 (d, J=11.6 Hz, 1H),4.84-4.81 (m, 4H), 4.81-4.78 (m, 2H), 4.76-4.73 (m, 2H), 4.73-4.70 (m,2H), 4.70 (d, J=5.0 Hz, 1H), 4.67 (bs, 2H), 4.63 (d, J=3.8 Hz, 1H),4.57-4.53 (m, 2H), 4.53-4.48 (m, 3H), 4.48 (d, J=3.5 Hz, 1H), 4.46 (d,J=2.5 Hz, 1H), 4.44 (d, J=3.0 Hz, 2H), 4.42-4.40 (m, 4H), 4.40-4.38 (m,4H), 4.35-4.29 (m, 2H), 4.29-4.24 (m, 4H), 4.24-4.18 (m, 4H), 4.18-4.15(m, 2H), 4.08-4.05 (m, 2H), 4.05-3.99 (m, 4H), 3.97 (d, J=10.4 Hz, 1H),3.88-3.87 (m, 6H), 3.81 (d, J=4.8 Hz, 2H), 3.77 (s, 3H), 3.75 (d, J=3.7Hz, 1H), 3.73 (d, J=3.5 Hz, 1H), 3.71 (d, J=3.5 Hz, 1H), 3.69-3.64 (m,2H), 3.62 (d, J=3.1 Hz, 1H), 3.60-3.58 (m, 2H), 3.58 (d, J=3.5 Hz, 1H),3.56 (t, J=9.7 Hz, 2H), 3.44 (t, J=9.7 Hz, 2H), 3.30 (d, J=3.7 Hz, 1H),3.28-3.23 (m, 1H), 2.01 (s, 6H), 1.99 (s, 3H), 1.97 (s, 3H); ¹³C NMR(CDCl₃) δ 170.5, 166.9, 166.8, 165.7, 165.5, 165.4, 155.2, 150.1, 137.7,137.6, 137.4, 137.2, 137.1, 133.4, 129.8, 129.7, 129.5, 129.4, 128.9,128.6, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.7, 127.6, 127.5,118.3, 114.5, 98.7, 98.3, 98.1, 98.0, 97.9, 97.8, 97.7, 97.5, 80.4,78.9, 78.7, 78.6, 77.7, 75.4, 75.3, 75.2, 75.1, 74.9, 74.6, 74.5, 74.3,74.2, 74.1, 74.0, 73.5, 72.4, 72.1, 70.3, 70.2, 70.1, 68.3, 67.7, 67.5,65.7, 64.9, 63.8, 63.7, 63.5, 62.6, 62.1, 55.7, 40.6, 40.5, 20.7.

Synthesis of 40

Compound 40 is prepared from compound 37 and compound 22 followinggeneral procedure E: 1.4 g, quant (beta), R_(f)=0.4 (Toluene/EtOAc 4:1).¹³C-NMR (125 MHz, CDCl₃) δ 170.6, 169.8, 166.6, 166.0, 165.9, 165.4,165.1, 155.6, 154.1, 151.0, 143.2, 142.9, 141.3, 141.2, 137.9, 137.7,137.3, 137.2, 137.0, 133.4, 133.2, 129.8, 129.7, 129.6, 129.5, 129.4,129.0, 128.6, 128.4, 128.3, 128.2, 128.15, 128.1, 128.0, 127.9, 127.8,127.7, 127.6, 125.3, 124.9, 120.0, 118.9, 114.5, 100.3, 98.3, 97.8,97.7, 97.6, 97.5, 97.1, 82.8, 78.6, 78.5, 75.3, 75.1, 74.9, 74.1, 74.0,73.8, 73.6, 73.4, 73.2, 72.7, 71.5, 70.5, 70.3, 70.1, 69.5, 68.6, 68.0,67.4, 63.5, 63.4, 62.9, 62.8, 62.5, 62.2, 62.0, 61.9, 59.3, 59.2, 55.6,46.7, 40.7, 20.7

Synthesis of 41

Compound 34 is prepared from compound 37 and compound 23 followinggeneral procedure E: 785 mg, 88% (beta), R_(f)=0.48 (toluene/EtOAc 4:1).¹³C-NMR (125 MHz, CDCl₃) δ 170.4, 166.9, 166.4, 165.1, 165.0, 164.9,155.7, 150.9, 138.2, 137.5, 137.2, 133.8, 133.7, 133.4, 129.8, 129.7,129.5, 129.0, 128.9, 128.8, 128.6, 128.5, 128.3, 128.2, 128.1, 128.0,127.7, 127.6, 127.5, 118.8, 114.5, 100.9, 100.8, 100.7, 100.0, 98.0,97.8, 97.8, 97.7, 82.8, 82.7, 80.1, 77.8, 77.7, 77.6, 75.6, 75.5, 75.4,75.2, 75.0, 74.9, 74.7, 74.6, 74.3, 74.2, 73.5, 72.4, 72.3, 70.3, 69.8,65.0, 64.4, 64.2, 63.2, 62.7, 62.7, 62.6, 62.4, 61.9, 61.8, 61.7, 55.6,40.5, 40.4, 40.3, 40.3, 20.7

Synthesis of 42

Compound 42 is prepared from compound 38 following general procedure D:The residue is purified by silica gel chromatography (EtOAc:petroleumether, 1:1) to furnish the disaccharide as a foam, 170 mg, 86% yield,R_(f)=0.45 (EtOAc:petroleum ether, 1:1). HRMS (ESI) calcd forC₁₅₅H₁₆₀Cl₄N₁₂O₅₀Na(M+Na)⁺ m/z 3151.8998, found 3151.8971. ¹H-NMR (500MHz, CDCl₃) δ 8.16 (dd, J=6.8 Hz, J=9.4 Hz, 2H), 8.11-8.07 (m, 6H),7.51-7.38 (m, 6 H), 7.37-7.27 (m, 5 H), 7.27-7.16 (m, 5 H), 7.46-7.38(m, 8 H), 7.37-7.22 (m, 10H), 7.21-7.18 (m, 12H), 7.15 (dd, J=6.1 Hz,J=8.4 Hz, 6H), 7.05 (d, J=8.9 Hz, 2H), 6.85 (d, J=9.1 Hz, 2H), 5.63 (bd,1H), 5.35 (t, J=3.4 Hz, 1H), 5.15-5.11 (m, 2H), 5.11-5.06 (m, 2H), 5.01(d, J=11.4 Hz, 1H), 4.85-4.79 (m, 2H), 4.78-4.74 (m, 5H), 4.74-4.66 (m,10H), 4.63 (d, J=4.1 Hz, 2H), 4.58-4.54 (m, 8H), 4.53 (d, J=6.8 Hz, 2H),4.51 (d, J=6.6 Hz, 4H), 4.47-4.43 (m, 6H), 4.43-4.39 (m, 4H), 4.36-4.26(m, 4H), 4.26-4.19 (m, 2H), 4.19-4.16 (m, 2H), 4.09-4.06 (m, 1H),4.05-3.99 (m, 2H), 3.97 (d, J=10.4 Hz, 1H), 3.89-3.86 (m, 4H), 3.82 (d,J=4.8 Hz, 2H), 3.76 (s, 3H), 3.75-3.71 (m, 2H), 3.71-3.65 (m, 2H),3.63-3.57 (m, 2H), 3.56 (t, J=10.1 Hz, 1H), 3.44 (t, J=9.7 Hz, 1H), 3.31(d, J=4.1 Hz, 1H), 3.29-3.24 (m, 2H), 2.01 (s, 3H), 2.01 (s, 3H), 2.0(s, 3H), 2.0 (s, 3H) ¹³C-NMR (125 MHz, CDCl₃) δ 169.9, 168.9, 168.74,168.7, 165.2, 164.9, 163.9, 163.7, 163.6, 153.4, 148.3, 135.9, 135.8,135.4, 135.37, 135.35, 131.7, 128.0, 127.9, 127.7, 127.6, 126.8, 126.7,126.6, 126.57, 126.5, 126.3, 126.28, 126.2, 125.9, 125.87, 125.8, 116.4,112.7, 97.1, 96.4, 96.3, 96.1, 95.9, 95.7, 77.9, 77.2, 76.9, 73.6, 73.5,73.47, 73.4, 73.3, 73.1, 72.8, 72.5, 72.3, 72.2, 71.6, 70.6, 70.3, 69.5,68.7, 68.5, 68.4, 66.5, 65.9, 65.8, 65.7, 63.9, 63.1, 62.0, 61.8, 61.7,61.6, 61.3, 60.9, 60.5, 60.3, 53.9, 38.8, 38.7, 18.9.

Synthesis of 136

Compound 136 is prepared from compound 137 following general procedureD: The residue is purified by silica gel chromatography (EtOAc:petroleumether, 2:3) to furnish the disaccharide as a foam, 890 mg, 229 μmol, 97%yield; TLC (EtOAc:petroleum ether, 1:1, v/v): R_(f)=0.45; HRMS (ESI)calcd for C₁₉₂H₁₉₈Cl₅N₁₅O₆₂ Na₂(M+2Na)²⁺ m/z 1965.054, found 1965.0496.¹H-NMR (500 MHz, CDCl₃) δ 8.16-8.13 (m, 2H), 8.12-8.07 (m, 6H),7.52-7.47 (m, 6 H), 7.45-7.39 (m, 12 H), 7.38-7.34 (m, 15 H), 7.32-7.27(m, 10 H), 7.27-7.22 (m, 8 H), 7.21-7.16 (m, 10H), 7.14-7.11 (m, 6H),7.05 (d, J=8.9 Hz, 2H), 6.85 (d, J=9.1 Hz, 2H), 5.62 (d, J=3.5 Hz, 1H),5.35 (d, J=3.4 Hz, 1H), 5.15-5.11 (m, 2H), 5.10-5.06 (m, 2H), 5.01 (d,J=11.4 Hz, 1H), 4.86-4.79 (m, 2H), 4.77-4.71 (m, 6H), 4.70-4.66 (m,10H), 4.63 (d, J=4.0 Hz, 1H), 4.58-4.53 (m, 6H), 4.53-4.51 (m, 2H), 4.50(d, J=3.5 Hz, 1H), 4.49-4.47 (m, 6H), 4.46-4.39 (m, 8H), 4.36-4.33 (m,4H), 4.32-4.27 (m, 6H), 4.26-4.21 (m, 4H), 4.20-4.15 (m, 3H), 4.13-4.12(m, 2H), 4.11 (d, J=7.1 Hz, 1H), 4.09-4.07 (m, 1H), 4.06-3.99 (m, 2H),3.97-3.95 (m, 1H), 3.94-3.93 (m, 1H), 3.88-3.87 (m, 4H), 3.87-3.86 (m,4H), 3.81 (d, J=5.0 Hz, 2H), 3.76 (s, 3H), 3.73-3.65 (m, 4H), 3.62-3.57(m, 2H), 3.56-3.52 (m, 2H), 3.40-3.35 (m, 2H), 3.31 (d, J=4.1 Hz, 1H),3.29-3.26 (m, 2H), 3.26 (d, J=4.3 Hz, 1H), 3.23 (d, J=3.7 Hz, 1H), 3.21(d, J=3.7 Hz, 1H), 2.94 (d, J=4.8 Hz, 1H), 2.03 (s, 3H), 2.02 (s, 3H),2.01 (s, 3H), 2.0 (s, 3H), 1.99 (s, 3H); ¹³C-NMR (125 MHz, CDCl₃) δ171.6, 171.1, 170.7, 170.6, 170.5, 167.0, 166.8, 165.7, 165.5, 155.2,150.2, 137.7, 137.6, 137.3, 137.2, 133.5, 129.9, 129.7, 129.5, 129.4,128.7, 128.6, 128.5, 128.4, 128.3, 128.1, 127.7, 127.6, 118.3, 114.6,98.9, 98.3, 98.1, 97.9, 97.8, 97.7, 97.5, 79.7, 78.9, 78.7, 75.4, 75.3,75.2, 75.1, 74.9, 74.6, 74.3, 74.1, 73.5, 72.4, 72.1, 71.3, 70.6, 70.5,70.4, 70.3, 70.2, 68.3, 67.8, 67.6, 67.5, 65.7, 64.9, 63.8, 63.6, 63.5,63.1, 62.8, 62.3, 62.1, 60.4, 55.7, 40.6, 40.5, 21.0, 20.7

Synthesis of 43

Compound 43 is prepared from compound 40 following general procedure D:960 mg, 72%, R_(f)=0.15 (toluene/EtOAc 7:3); ¹³C-NMR (125 MHz, CDCl₃) δ171.9, 170.5, 170.4, 166.9, 166.4, 165.1, 165.0, 164.9, 155.7, 150.9,138.3, 138.2, 138.0, 137.8, 137.3, 137.2, 133.7, 133.5, 129.8, 129.5,129.0, 128.95, 128.9, 128.8, 128.7, 128.6, 128.4, 128.3, 128.2, 128.1,127.7, 127.5, 127.45, 127.3, 127.0, 125.3, 118.8, 114.5, 100.9, 100.8,100.7, 100.0, 98.3, 97.8, 97.7, 82.9, 82.8, 82.7, 79.2, 77.7, 77.65,77.6, 76.55, 75.4, 75.0, 74.9, 74.7, 74.6, 74.3, 73.6, 72.5, 72.3, 71.4,70.6, 69.8, 64.9, 64.4, 64.2, 62.7, 62.6, 61.9, 61.8, 61.7, 55.6, 40.4,40.3, 20.7

Synthesis of 44

Compound 44 is prepared from compound 42 and compound 25 followinggeneral procedure E: The residue is purified by silica gelchromatography (EtOAc:petroleum ether, 1:2) to furnish the disaccharideas a foam, 173 mg, 89% yield, R_(f)=0.23 (EtOAc:petroleum ether, 1:2).HRMS (ESI) calcd for C₁₉₉H₂₀₄Cl₅N₁₅O₆₂Na(M+Na)⁺ m/z 3993.16, found3993.1611. ¹H-NMR (500 MHz, CDCl₃) δ 8.16 (dd, J=7.0 Hz, J=9.7 Hz, 2 H),8.11-8.07 (m, 6 H), 7.51-7.47 (m, 8 H), 7.45-7.38 (m, 10 H), 7.37-7.33(m, 14 H), 7.33-7.27 (m, 12H), 7.26-7.19 (m, 10H), 7.18-7.16 (m, 10H),7.14-7.12 (m, 8H), 7.05 (d, J=9.1 Hz, 2H), 6.85 (d, J=9.1 Hz, 2H), 5.63(d, J=4.0 Hz, 1H), 5.35 (t, J=3.8 Hz, 2H), 5.15-5.11 (m, 2H), 5.10-5.06(m, 2H), 5.01 (d, J=11.4 Hz, 1H), 4.85-4.82 (m, 4H), 4.81-4.79 (m, 2H),4.78-4.74 (m, 2H), 4.73-4.71 (m, 4H), 4.71-4.69 (m, 1H), 4.68-4.66 (m,10H), 4.63 (d, J=3.9 Hz, 1H), 4.58-4.53 (m, 10H), 4.53-4.51 (m, 6H),4.51 (d, J=3.9 Hz, 1H), 4.49-4.47 (m, 2H), 4.46-4.43 (m, 6H), 4.43-4.41(m, 6H), 4.41-4.39 (m, 2H), 4.35-4.26 (m, 2H), 4.25-4.20 (m, 4H),4.19-4.16 (m, 4H), 4.09-3.99 (m, 2H), 3.97 (d, J=9.9 Hz, 1H), 3.89-3.86(m, 8H), 3.82 (d, J=5.4 Hz, 2H), 3.76 (s, 3H), 3.75 (bd, 1H), 3.74 (bd,1H), 3.72 (bd, 1H), 3.70-3.65 (m, 2H), 3.63-3.58 (m, 2H), 3.58 (d, J=3.6Hz, 1H), 3.56 (t, J=9.2 Hz, 1H), 3.44 (t, J=9.6 Hz, 2H), 3.31 (d, J=4.1Hz, 1H), 3.29-3.27 (m, 1H), 3.27-3.24 (m, 1H), 2.014 (s, 3H), 2.012 (s,3H), 2.0 (s, 3H), 1.99 (s, 3H), 1.97 (s, 3H); ¹³C NMR (CDCl₃) δ 168.8,168.7, 168.6, 168.5, 165.1, 165.0, 164.9, 163.9, 163.7, 163.6, 163.5,153.4, 148.4, 135.9, 135.8, 135.7, 135.5, 135.4, 135.3, 131.7, 131.6,128.3, 128.1, 127.9, 127.7, 126.9, 126.8, 126.7, 126.6, 126.5, 126.4,126.3, 126.2, 126.1, 125.9, 125.8, 116.5, 112.8, 96.9, 96.5, 96.3, 96.2,96.1, 95.9, 95.8, 95.7, 78.6, 77.2, 77.0, 76.9, 75.9, 75.6, 75.3, 73.6,73.5, 73.4, 73.3, 73.1, 72.8, 72.7, 72.5, 72.3, 71.7, 71.6, 70.6, 70.3,68.6, 68.5, 68.4, 68.3, 66.5, 65.9, 65.8, 65.7, 65.6, 63.9, 63.1, 62.1,61.9, 61.8, 61.7, 60.8, 60.5, 60.3, 53.9, 38.9, 38.7, 20.9.

Synthesis of 137

Compound 137 is prepared from compound 24 and compound 42 followinggeneral procedure E: 1.16 g, 0.282 mmol, 86% yield; TLC,(EtOAc:petroleum ether, 1:2 v/v): R_(f)=0.2. HRMS (ESI) calcd forC₂₀₇H₂₀₈Cl₅N₁₅O₆₄Na(M+Na)⁺ m/z 4129.1865, found 4129.1802. ¹H-NMR (500MHz, CDCl₃) δ 8.17 (dd, J=6.7 Hz, J=9.6 Hz, 2 H), 8.12-8.08 (m, 4 H),7.75 (d, J=2.5 Hz, 2H), 7.73 (d, J=2.5 Hz, 2H), 7.59 (d, J=7.4 Hz, 2H),7.54 (d, J=7.6 Hz, 2H), 7.50-7.45 (m, 10H), 7.44-7.38 (m, 14 H),7.37-7.29 (m, 12H), 7.28-7.21 (m, 10H), 7.20-7.17 (m, 8H), 7.16-7.13 (m,4H), 7.08-7.06 (m, 3H), 7.06 (d, J=9.0 Hz, 2H), 6.85 (d, J=9.0 Hz, 2H),5.63 (d, J=3.7 Hz, 1H), 5.35 (t, J=3.6 Hz, 2H), 5.17-5.07 (m, 5H), 5.01(d, J=12.0 Hz, 1H), 4.88-4.81 (m, 8H), 4.78-4.68 (m, 10H), 4.59-4.53 (m,6H), 4.53 (d, J=5.0 Hz, 1H), 4.51 (d, J=5.0 Hz, 1H), 4.49-4.41 (m, 8H),4.41-4.37 (m, 12H), 4.36-4.28 (m, 8H), 4.28-4.22 (m, 6H), 4.21-4.18 (m,4H), 4.17-4.13 (m, 4H), 4.11-4.0 (m, 3H), 3.98 (d, J=10.5 Hz, 1H),3.91-3.87 (m, 6H), 3.81 (d, J=5.0 Hz, 2H), 3.73 (s, 3H), 3.71-3.65 (m,2H), 3.64-3.58 (m, 2H), 3.58-3.52 (m, 2H), 3.32-3.26 (m, 3H), 2.03 (s,3H), 2.01 (s, 6H), 2.0 (s, 3H), 1.99 (3H); ¹³C-NMR (125 MHz, CDCl₃) δ170.6, 170.5, 166.8, 165.7, 165.6, 165.5, 155.2, 154.2, 150.2, 143.2,143.1, 141.4, 137.7, 137.6, 137.3, 137.2, 137.1, 133.5, 129.9, 129.8,129.6, 129.5, 128.8, 128.7, 128.5, 128.4, 128.3, 128.2, 128.0, 127.9,127.8, 127.3, 125.1, 124.8, 120.2, 118.3, 114.6, 98.8, 98.3, 98.2, 98.1,97.9, 97.8, 97.5, 79.1, 78.9, 78.8, 75.4, 75.3, 75.1, 75.0, 74.7, 74.6,74.2, 74.0, 73.9, 73.5, 73.4, 72.4, 72.1, 70.4, 70.3, 69.8, 68.8, 67.6,67.2, 66.4, 65.7, 64.9, 63.9, 63.7, 63.6, 63.2, 62.4, 62.2, 62.0, 60.4,55.7, 40.7, 40.6, 20.8, 20.7.

Synthesis of 138

Compound 138 is prepared from compound 25 and compound 136 followinggeneral procedure E: The residue is purified by silica gelchromatography (EtOAc:petroleum ether, 1:2) to furnish the disaccharideas a foam, 780 mg, 0.165 mmol, 92% yield; TLC (EtOAc:petroleum ether,1:2, v/v): R_(f)=0.18; HRMS (ESI) calcd forC₂₃₆H₂₄₂Cl₆N₁₈O₇₄Na₂(M+2Na)²⁺ m/z 2386.1851, found 2386.1833. ¹H-NMR(500 MHz, CDCl₃) δ 8.16 (dd, J=7.0 Hz, J=9.6 Hz, 2 H), 8.12-8.07 (m, 6H), 7.51-7.46 (m, 8 H), 7.45-7.37 (m, 12 H), 7.37-7.34 (m, 18 H),7.34-7.29 (m, 22H), 7.29-7.27 (m, 12H), 7.26-7.20 (m, 10H), 7.20-7.16(m, 10H), 7.15-7.12 (m, 5H), 7.06 (d, J=9.2 Hz, 2H), 6.85 (d, J=9.2 Hz,2H), 5.63 (d, J=4.0 Hz, 1H), 5.35 (t, J=3.9 Hz, 2H), 5.17-5.06 (m, 6H),5.0 (d, J=12.0 Hz, 1H), 4.86-4.79 (m, 12H), 4.81-4.79 (m, 10H),4.78-4.66 (m, 14H), 4.65 (d, J=4.6 Hz, 1H), 4.59-4.54 (m, 6H), 5.54 (t,J=10.2 Hz, 2H), 4.48-4.40 (m, 10H), 4.37-4.27 (m, 8H), 4.27-4.20 (m,6H), 4.20-4.17 (m, 4H), 4.10-4.0 (m, 4H), 3.97-3.95 (m, 1H), 3.95-3.93(m, 2H), 3.93-3.91 (m, 3H), 3.90-3.87 (m, 4H), 3.86-3.84 (m, 6H), 3.82(d, J=4.2 Hz, 6H), 3.74 (s, 3H), 3.73-3.71 (m, 1H), 3.70-3.67 (m, 2H),3.64-3.58 (m, 3H), 3.57-3.52 (m, 2H), 3.45-3.40 (m, 2H), 3.33-3.25 (m,3H), 2.01 (s, 6H), 2.0 (s, 6H), 1.99 (s, 3H), 1.97 (s, 3H); ¹³C-NMR (125MHz, CDCl₃) δ 170.7, 170.6, 170.5, 167.0, 166.9, 166.8, 165.8, 165.7,165.6, 155.4, 150.3, 137.8, 137.7, 137.6, 137.4, 137.3, 133.6, 133.5,129.9, 129.8, 129.6, 128.8, 128.7, 128.6, 128.5, 128.4, 128.36, 128.3,128.2, 128.1, 128.0, 127.8, 127.7, 118.4, 116.6, 114.7, 98.9, 98.4,98.3, 98.2, 98.1, 98.0, 97.9, 97.7, 91.9, 80.5, 79.1, 78.9, 78.8, 77.4,77.1, 76.9, 75.5, 75.4, 75.3, 75.2, 75.1, 75.0, 74.7, 74.6, 74.3, 74.2,73.6, 73.5, 72.5, 72.3, 70.5, 70.4, 70.2, 68.6, 68.4, 67.7, 67.6, 66.6,66.5, 66.4, 66.3, 65.0, 63.9, 63.8, 63.7, 63.6, 62.7, 62.4, 62.3, 55.7,40.8, 40.7, 19.3.

Synthesis of 45

Compound 45 is prepared from compound 43 and compound 23 followinggeneral procedure E: 1.05 g, 89% (beta), R_(f)=0.46 (Toluene/EtOAc 4:1).¹³C-NMR (125 MHz, CDCl₃) δ 170.45, 170.44, 170.43, 170.38, 166.9, 166.4,166.4, 165.1, 165.0, 164.9, 155.7, 150.9, 138.3, 138.26, 138.25 137.9,137.5, 137.35, 137.3, 137.28, 137.26, 133.8, 133.7, 133.5, 129.8, 129.7,129.5, 129.1, 129.0, 128.9, 128.8, 128.62, 128.59, 128.57, 128.4, 128.3,128.2, 128.1, 128.0, 127.7, 127.6, 127.5, 127.4, 118.8, 114.5, 100.9,100.8, 100.7 (2C), 100.0, 98.1, 97.9, 97.8 (2C), 97.7, 82.8, 82.7, 80.1,77.8, 77.7, 77.6, 77.6, 77.5, 75.6, 75.5, 75.4, 75.2, 75.2, 75.1, 74.9,74.7, 74.6, 74.3, 74.2, 74.2, 73.6, 72.4, 72.3, 70.4, 69.8, 65.0, 64.4,64.2, 63.2, 62.7, 62.7, 62.6, 62.4, 61.9, 61.8, 61.7, 55.6, 40.5, 40.4,40.3, 40.3, 20.8, 20.7

General Procedure F (GPF): Selective De-chloroacetylation. DABCO (6equiv. per chloroacetyl group) is added to the starting material in dryethanol (5 mL for 40 μmol) at room temperature. The mixture is heated at60-70° C. under argon for 2 h. After TLC (EtOAc:petroleum ether, 3:2)indicated the completion of the reaction Dowex 50WX8-200 ion-exchangeresin is added to neutralize the solution. After 15 min the resin isfiltered off and the solution is concentrated to dryness. Chromatography(EtOAc:petroleum ether, 3:2) affords the products with unblocked primaryhydroxyl groups.

Synthesis of 46

Compound 46 is prepared from compound 33 following general procedure F:The residue is purified by silica gel chromatography (EtOAc:petroleumether, 1:1) to furnish the disaccharide as a foam, 330 mg, 98% yield,R_(f)=0.2 (EtOAc:petroleum ether, 1:1). HRMS (ESI) calcd forC₁₁₉H₁₂₅N₉O₃₅Na (M+Na)⁺ m/z 2262.8176, found 2262.8201. ¹H-NMR (500 MHz,CDCl₃) δ 8.15 (dd, J=6.2 Hz, J=9.6 Hz, 2 H), 8.10-8.07 (m, 4 H),7.47-7.44 (m, 4 H), 7.43-7.41 (m, 6 H), 7.40-7.38 (m, 4H), 7.37-7.32 (m,4 H), 7.31-7.25 (m, 6H), 7.24-7.21 (m, 8H), 7.20-7.17 (m, 6H), 7.16-7.14(m, 6H), 7.06 (d, J=9.5 Hz, 2H), 6.85 (d, J=8.9 Hz, 2H), 5.64 (d, J=4.0Hz, 1H), 5.37 (t, J=3.1 Hz, 2H), 5.15 (t, J=3.3 Hz, 2H), 5.12 (t, J=2.6Hz, 2H), 5.06 (d, J=2.6 Hz, 1H), 5.02 (d, J=6.6 Hz, 1H), 4.98 (bs, 1H),4.88 (d, J=5.7 Hz, 1H), 4.85 (d, J=6.2 Hz, 1H), 4.82 (d, J=11.9 Hz, 1H),4.76 (d, J=2.7 Hz, 1H), 4.74 (d, J=2.7 Hz, 1H), 4.72 (t, J=3.0 Hz, 2H),4.68 (d, J=3.7 Hz, 1H), 4.63 (d, J=4.0 Hz, 1H), 4.51 (d, J=5.5 Hz, 1H),4.49-4.46 (m, 2H), 4.46-4.44 (m, 2H), 4.39 (d, J=10.2 Hz, 1H), 4.33 (d,J=2.7 Hz, 1H), 4.31 (d, J=2.7 Hz, 1H), 4.29-4.25 (m, 2H), 4.25-4.21 (m,2H), 4.25-4.17 (m, 2H), 4.16 (d, J=4.7 Hz, 1H), 4.14-4.10 (m, 1H), 4.05(q, J=3.7 Hz, 2H), 3.98 (d, J=10.5 Hz, 1H), 3.96-3.93 (m, 1H), 3.87-3.82(m, 1H), 3.79-3.76 (m, 3H), 3.75 (s, 3H), 3.73 (d, J=2.4 Hz, 1H), 3.68(d, J=4.0 Hz, 1H), 3.66 (d, J=9.2 Hz, 1H), 3.62-3.57 (m, 1H), 3.57 (d,J=3.6 Hz, 1H), 3.53 (q, J=7.6 Hz, 2H), 3.42 (t, J=9.3 Hz, 2H), 3.35 (d,J=3.8 Hz, 1H), 3.33 (d, J=3.8 Hz, 1H), 3.32 (d, J=3.8 Hz, 1H), 3.30 (d,J=3.8 Hz, 1H), 3.28 (d, J=3.8 Hz, 1H), 3.27 (d, J=3.6 Hz, 1H), 3.25-3.22(m, 1H), 2.01 (s, 3H), 2.00 (s, 3H), 1.98 (s, 3H); ¹³C-NMR (125 MHz,CDCl₃) δ 170.6, 170.5, 165.8, 165.7, 155.2, 150.4, 137.7, 137.6, 137.5,137.4, 133.4, 133.3, 129.9, 129.8, 129.7, 129.6, 128.7, 128.6, 128.5,128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.5, 118.3,114.7, 98.2, 97.9, 97.8, 97.7, 97.3, 97.2, 80.6, 79.3, 79.2, 77.8, 77.6,76.8, 75.2, 75.1, 75.0, 74.6, 74.2, 74.0, 73.9, 73.4, 73.3, 73.2, 73.0,72.9, 72.9, 72.3, 72.1, 70.5, 70.1, 70.0, 69.5, 69.2, 68.9, 68.1, 67.9,67.8, 64.1, 63.9, 63.8, 63.1, 62.8, 62.7, 62.4, 61.6, 61.2, 61.1, 55.7,20.8, 20.7.

Synthesis of 47

Compound 47 is prepared from compound 35 following general procedure F:342 mg, 74%, R_(f)=0.17 (Toluene/EtOAc 7:3). ¹³C-NMR (125 MHz, CDCl₃) δ170.6, 170.4, 165.0, 155.6, 151.1, 138.2, 138.1, 137.8, 137.6, 137.4,137.3, 133.6, 133.5, 133.3, 129.8, 129.6, 129.1, 129.0, 128.7, 128.6,128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 128.0, 127.9, 127.7, 127.6,127.5, 127.2, 127.1, 118.4, 114.6, 101.1, 101.0, 100.4, 97.6, 97.3,97.2, 83.5, 83.35, 83.3, 80.3, 78.0, 77.9, 77.8, 77.7, 77.6, 75.5, 75.2,75.1, 75.0, 74.9, 74.8, 74.5, 74.4, 73.9, 73.4, 73.3, 72.3, 70.0, 69.6,69.5, 63.2, 62.9, 62.7, 62.6, 62.2, 62.1, 61.8, 61.5, 61.4, 55.6, 20.8

Synthesis of 48

Compound 48 is prepared from compound 39 following general procedure F:The residue is purified by silica gel chromatography (EtOAc:petroleumether, 3:2) to furnish the disaccharide as a foam, 99 mg, 84% yield,R_(f)=0.25 (EtOAc:petroleum ether, 3:2). HRMS (ESI) calcd forC₁₅₄H₁₆₂N₁₂O₄₆Na (M+Na)⁺ m/z 2938.0604, found 2938.0603. ¹H-NMR (500MHz, CDCl₃) δ 8.15 (dd, J=6.1 Hz, J=9.7 Hz, 2 H), 8.10-8.07 (m, 4 H),7.46-7.44 (m, 4 H), 7.43-7.39 (m, 6 H), 7.39-7.36 (m, 4H), 7.36-7.33 (m,4 H), 7.33-7.30 (m, 6H), 7.30-7.26 (m, 8H), 7.24-7.21 (m, 2H), 7.20-7.17(m, 6H), 7.16-7.14 (m, 6H), 7.07 (d, J=9.5 Hz, 2H), 6.84 (d, J=9.1 Hz,2H), 5.64 (d, J=4.0 Hz, 1H), 5.36 (t, J=3.1 Hz, 2H), 5.15 (t, J=2.6 Hz,2H), 5.13-5.10 (m, 2H), 5.07 (dd, J=4.2 Hz, J=7.8 Hz, 2H), 5.02 (d,J=12.5 Hz, 1H), 4.88 (d, J=7.2 Hz, 1H), 4.86 (bd, 1H), 4.85 (d, J=2.7Hz, 1H), 4.82 (d, J=11.7 Hz, 1H), 4.77 (d, J=5.8 Hz, 1H), 4.74 (d, J=3.8Hz, 1H), 4.72 (d, J=5.3 Hz, 1H), 4.68 (d, J=3.5 Hz, 1H), 4.63 (d, J=4.1Hz, 1H), 4.51 (bs, 1H), 4.49 (t, J=3.8 Hz, 2H), 4.46 (d, J=3.5 Hz, 1H),4.39 (d, J=10.6 Hz, 1H), 4.33-4.30 (m, 5H), 4.28-4.25 (m, 3H), 4.24-4.21(m, 4H), 4.21-4.16 (m, 6H), 4.16-4.11 (m, 5H), 4.05 (q, J=3.7 Hz, 2H),4.01-4.0 (m, 3H), 3.98-3.93 (m, 3H), 3.87-3.82 (m, 2H), 3.81-3.76 (m,3H), 3.75 (s, 3H), 3.74 (d, J=6.1 Hz, 1H), 3.68 (d, J=9.1 Hz, 1H), 3.66(d, J=9.0 Hz, 1H), 3.64 (bs, 1H), 3.63-3.57 (m, 1H), 3.57-3.54 (m, 1H),3.53-3.45 (m, 2H), 3.42 (t, J=9.8 Hz, 2H), 3.35 (d, J=3.8 Hz, 1H), 3.34(q, J=2.2 Hz, 2H), 3.32 (d, J=3.7 Hz, 1H), 3.30 (d, J=4.0 Hz, 1H), 3.28(d, J=3.6 Hz, 1H), 3.26 (d, J=3.7 Hz, 1H), 3.25-3.18 (m, 1H), 2.01 (s,3H), 2.01 (s, 6H), 2.01 (s, 3H), 1.98 (s, 3H); ¹³C-NMR (125 MHz, CDCl₃)δ 170.6, 170.5, 165.8, 165.5, 155.2, 150.4, 137.7, 137.4, 137.3, 133.3,130.8, 129.8, 129.7, 129.6, 128.6, 128.5, 128.4, 128.2, 128.0, 127.9,127.8, 118.4, 114.7, 98.2, 97.9, 97.4, 97.3, 80.6, 79.3, 79.2, 77.9,77.4, 76.8, 75.2, 75.1, 75.0, 74.6, 74.2, 74.0, 73.9, 73.8, 73.3, 73.2,73.15, 73.1, 72.9, 72.3, 72.1, 70.5, 70.1, 70.0, 69.5, 69.2, 69.1, 68.9,68.0, 67.9, 67.8, 67.7, 64.1, 64.0, 63.8, 62.8, 62.7, 62.4, 61.6, 61.2,61.1, 55.6, 20.8.

Synthesis of 49

Compound 49 is prepared from compound 41 following general procedure F:820 mg, 95%, R_(f)=0.1 (Toluene/EtOAc 7:3). ¹³C-NMR (125 MHz, CDCl₃) δ170.6, 170.4, 165.0, 155.6, 151.1, 138.24, 138.2, 138.17, 137.9, 137.6,137.44, 137.4, 133.7, 133.6, 133.4, 129.8, 129.6, 129.1, 129.0, 128.7,128.6, 128.5, 128.3, 128.2, 128.1, 128.0, 128.0, 127.9, 127.7, 127.6,127.2, 127.1, 118.4, 114.6, 101.1, 101.0, 100.9, 100.4, 97.6, 97.3,97.2, 83.5, 83.4, 83.35, 80.3, 78.0, 77.9, 77.8, 77.7, 77.6, 75.6, 75.2,75.1, 75.0, 74.9, 74.8, 74.5, 74.4, 73.9, 73.5, 73.4, 72.3, 70.0, 69.6,69.5, 63.2, 62.9, 62.8, 62.7, 62.6, 62.2, 62.0, 61.8, 61.5, 61.4, 61.3,55.6, 20.8

Synthesis of 50

Compound 50 is prepared from compound 44 following general procedure F:The residue is purified by silica gel chromatography (EtOAc:petroleumether, 3:2) to furnish the disaccharide as a foam, 115 mg, 83% yield,Rf=0.25 (EtOAc:petroleum ether, 3:2). HRMS (ESI) calcd forC₁₈₉H₁₉₉N₁₅O₅₇Na(M+Na)⁺ m/z 3613.3085, found 3613.3083. ¹H-NMR (500 MHz,CDCl₃) δ 8.15 (dd, J=6.4 Hz, J=9.1 Hz, 2 H), 8.10-8.07 (m, 6 H),7.47-7.44 (m, 4 H), 7.43-7.40 (m, 6 H), 7.40-7.36 (m, 10H), 7.37-7.32(m, 8 H), 7.32-7.30 (m, 12H), 7.30-7.25 (m, 12H), 7.24-7.21 (m, 8H),7.20-7.16 (m, 6H), 7.16-7.14 (m, 6H), 7.07 (d, J=9.1 Hz, 2H), 6.84 (d,J=9.1 Hz, 2H), 5.65 (d, J=4.0 Hz, 1H), 5.37 (t, J=3.1 Hz, 2H), 5.15-5.10(m, 6H), 5.06-5.02 (m, 4H), 5.02 (d, J=11.1 Hz, 1H), 4.88-4.83 (m, 3H),4.82 (d, J=12.3 Hz, 1H), 4.77 (d, J=4.6 Hz, 1H), 4.74-4.70 (m, 10H),4.68-4.65 (m, 12H), 4.63 (d, J=3.8 Hz, 1H), 4.51 (bs, 1H), 4.49-4.43 (m,6H), 4.39 (d, J=10.3 Hz, 1H), 4.33-4.30 (m, 6H), 4.26-4.21 (m, 3H),4.21-4.17 (m, 6H), 4.16-4.10 (m, 3H), 4.05-4.0 (m, 3H), 3.99-3.94 (m,3H), 3.87-3.82 (m, 2H), 3.81-3.77 (m, 3H), 3.76 (s, 3H), 3.75-3.72 (m,1H), 3.68 (d, J=9.0 Hz, 1H), 3.66 (d, J=9.0 Hz, 1H), 3.62-3.57 (m, 1H),3.57-3.53 (m, 1H), 3.52-3.45 (m, 2H), 3.41 (t, J=8.1 Hz, 2H), 3.35 (d,J=3.8 Hz, 1H), 3.34 (d, J=3.6 Hz, 1H), 3.32 (d, J=3.7 Hz, 1H), 3.30 (dd,J=4.0 Hz, J=9.0 Hz, 2H), 3.29 (t, J=5.6 Hz, 2H), 3.27 (d, J=3.8 Hz, 1H),3.24-3.18 (m, 1H), 2.009 (s, 6H), 2.004 (s, 6H), 1.98 (s, 3H); ¹³C-NMR(125 MHz, CDCl₃) δ 170.6, 170.5, 165.9, 165.8, 165.7, 155.3, 150.4,137.7, 137.6, 137.5, 137.4, 133.4, 133.3, 130.9, 129.9, 129.84, 129.8,129.7, 129.66, 129.6, 128.6, 128.58, 128.57, 128.5, 128.47, 128.4,128.23, 128.22, 128.18, 128.14, 128.1, 128.0, 127.9, 127.93, 127.9,127.8, 118.4, 114.7, 98.2, 98.1 (3C), 97.9 (3C), 97.8, 97.7, 97.3, 80.6,79.3, 79.2, 77.8, 77.4, 77.1, 76.9, 75.2, 75.1, 75.0, 74.6, 74.2, 74.0,73.9, 73.8, 73.5, 73.4, 73.3, 73.2, 73.1, 73.0, 72.9, 72.3, 72.1, 70.5,70.1, 70.05, 70.0, 69.5, 69.2, 69.1, 68.9, 68.0, 67.9, 67.8, 67.7, 64.1,64.0, 63.8, 62.8, 62.4, 61.6, 61.2, 61.1, 61.0, 55.7, 20.8.

Synthesis of 139

Compound 139 is prepared from compound 138 following general procedureF: The residue is purified by silica gel chromatography (EtOAc:toluene,3:2) to furnish the disaccharide as a foam (518 mg, 121 μmol, 80%yield); TLC (EtOAc:petroleum ether, 3:2, v/v) R_(f)=0.22; HRMS (ESI)calcd for C₂₂₄H₂₃₆N₁₈O₆₈Na₂(M+2Na)²⁺ m/z 2156.7711, found 2156.7732.¹H-NMR (500 MHz, CDCl₃) δ 8.16 (dd, J=6.0 Hz, J=9.7 Hz, 2 H), 8.12-8.08(m, 6 H), 7.47 (d, J=7.2 Hz, 2 H), 7.43-7.38 (m, 12 H), 7.37-7.31 (m,14H), 7.31-7.24 (m, 18 H), 7.24-7.21 (m, 22H), 7.21-7.16 (m, 14H),7.16-7.10 (m, 5H), 7.07 (d, J=9.0 Hz, 2H), 6.84 (d, J=9.0 Hz, 2H), 5.64(d, J=4.0 Hz, 1H), 5.37 (t, J=3.3 Hz, 2H), 5.17-5.11 (m, 6H), 5.08-5.05(m, 4H), 5.04-5.02 (m, 1H), 5.01 (d, J=11.0 Hz, 1H), 4.89-4.83 (m, 5H),4.82 (d, J=11.7 Hz, 1H), 4.77-4.76 (m, 1H), 4.75-4.73 (m, 8H), 4.73-4.71(m, 6H), 4.71-4.69 (m, 4H), 4.69-4.65 (m, 12H), 4.62 (d, J=3.9 Hz, 1H),4.52-4.43 (m, 8H), 4.40 (d, J=11.0 Hz, 1H), 4.35-4.23 (m, 7H), 4.23-4.12(m, 8H), 4.07-4.01 (m, 4H), 3.98 (d, J=10.3 Hz, 1H), 3.88-3.79 (m, 6H),3.79-3.73 (m, 3H), 3.72 (s, 3H), 3.69-3.66 (m, 2H), 3.65-3.58 (m, 2H),3.58-3.55 (m, 2H), 3.54-3.46 (m, 4H), 3.41 (t, J=9.1 Hz, 2H), 3.35-3.29(m, 4H), 3.29-3.27 (m, 2H), 3.27-3.20 (m, 5H), 2.0 (s, 12H), 1.99 (s,3H), 1.97 (s, 3H); ¹³C-NMR (125 MHz, CDCl₃) δ 170.6, 170.5, 165.9,165.8, 165.7, 155.3, 150.5, 137.9, 137.8, 137.6, 137.5, 137.4, 133.4,130.0, 129.9, 129.7, 129.1, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1,127.9, 127.8, 125.4, 118.4, 114.7, 98.2, 97.9, 97.8, 97.4, 80.7, 79.4,79.3, 77.0, 75.2, 75.1, 74.7, 74.3, 74.1, 73.9, 73.8, 73.4, 73.2, 73.0,72.9, 72.3, 72.1, 70.5, 70.2, 69.6, 69.3, 69.2, 68.9, 68.1, 67.9, 67.8,64.2, 64.1, 63.8, 62.8, 62.5, 61.6, 61.2, 55.7, 20.8, 20.7.

Synthesis of 51

Compound 51 is prepared from compound 45 following general procedure F:760 mg, 92%, R_(f)=0.07 (Toluene/EtOAc 7:3). ¹³C-NMR (125 MHz, CDCl₃) δ170.6, 170.5, 170.45, 170.4, 165.0, 155.6, 151.1, 138.3, 138.2, 138.1,137.9, 137.6, 137.4, 137.3, 133.7, 133.6, 133.4, 129.8, 129.6, 129.1,129.0, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 128.0,127.9, 127.8, 127.7, 127.6, 127.2, 127.1, 118.4, 114.6, 101.1, 101.0,100.9 (2C), 100.4, 97.6, 97.3 (3C), 97.2, 83.5, 83.4, 83.35, 80.3, 78.0,77.9, 77.8, 77.7, 77.6, 77.5, 75.6, 75.3, 75.2, 75.1, 75.0, 74.9, 74.8,74.6, 74.5, 74.4, 73.9, 73.5, 73.45, 73.4, 72.3, 70.0, 69.6, 69.5, 63.3,62.9, 62.8, 62.7, 62.6, 62.2, 62.0, 61.8, 61.5, 61.4, 61.3, 55.6, 20.8

General Procedure G1 (GPG1): TEMPO/BAIB Oxidation and Esterification byDiazomethane.

A solution of starting material in acetonitrile (5 mL for 32 μmol) andwater (0.9 mL) is treated with TEMPO (0.2 equiv.) and BAIB (2.5 equiv.per hydroxyl group) at room temperature for 4-24 hours. After TLC(EtOAc:petroleum ether, 3:2) indicates the completion of the reactionchloroform and water are added. The solution is acidified with dilutedHCl, back-extracted with chloroform, dried and concentrated. The residueis dissolved in dry ether and treated with an excess of freshly prepareddiazomethane solution in ether until TLC (EtOAc:petroleum ether, 2:3)indicates the formation of methyl esters. The residues are purified bysilica gel chromatography (EtOAc:petroleum ether, 2:3) to furnish theesters.

General Procedure G2 (GPG2): TEMPO/BAIB Oxidation and Esterificationwith TMS-Diazomethane.

A solution of starting material in acetonitrile (5 mL for 32 μmol) andwater (0.9 mL) is treated with TEMPO (0.2 equiv.) and BAIB (2.5 equiv.per hydroxyl group) at room temperature for 4-24 hours. After TLC(EtOAc:petroleum ether, 3:2) indicated the completion of the reactionchloroform and water are added. The solution is acidified with dilutedHCl, back-extracted with chloroform, dried and concentrated. The residueis dissolved in diethyl ether/methanol (3:2) and and a 2M solution ofTMS-diazomethane in hexane (1.5 eq per carboxylate) is added dropwise at0° C. After completion (TLC:Tol/EtOAc 3:2), 0.5 mL acetic acid are addedto quench the reaction. Solvents are evaporated in vacuo and theresidues are purified by silica gel chromatography to furnish theesters.

General Procedure G3 (GPG3): TEMPO/BAIB Oxidation and Esterificationwith Iodomethane

A solution of starting material in acetonitrile (5 mL for 32 μmol) andwater (0.9 mL) is treated with TEMPO (0.2 equiv.) and BAIB (2.5 equiv.per hydroxyl group) at room temperature for 4-24 hours. After TLC(EtOAc:petroleum ether, 3:2) indicates the completion of the reactionchloroform and water are added. The solution is acidified with dilutedHCl, back-extracted with chloroform, dried and concentrated. The residueis dissolved in anhydrous DMF (100 mL per mmol). Potassium bicarbonate(20 eq) and iodomethane (15 eq) are added and the mixture is stirred atambient temperature for 12-24 h. The reaction mixture is concentratedand partitioned between ethyl acetate and water, washed with brine,dried over magnesium sulfate and concentrated. Purification on silicagel furnishes the esters.

Synthesis of 52

Compound 52 is prepared from compound 46 following general procedure G1:The residue is purified by silica gel chromatography (EtOAc:petroleumether, 1:2) to furnish the disaccharide as a foam, 280 mg, 82% yield,R_(f)=0.75 (EtOAc:petroleum ether, 1:1). HRMS (ESI) calcd forC₁₂₂H₁₂₅N₉O₃₈Na(M+Na)⁺ m/z 2346.8023, found 2346.8005. ¹H-NMR (500 MHz,CDCl₃) δ 8.13-8.10 (m, 4 H), 8.09 (dd, J=7.1 Hz, J=9.3 Hz, 2H),7.55-7.47 (m, 4 H), 7.47-7.40 (m, 6 H), 7.37-7.32 (m, 4H), 7.31-7.28 (m,4 H), 7.28-7.26 (m, 6H), 7.25-7.22 (m, 8H), 7.18-7.15 (m, 6H), 7.15-7.12(m, 6H), 7.03 (d, J=8.7 Hz, 2H), 6.81 (d, J=9.4 Hz, 2H), 5.72 (d, J=3.9Hz, 1H), 5.49 (d, J=4.9 Hz, 1H), 5.45 (d, J=5.4 Hz, 1H), 5.32 (t, J=2.3Hz, 2H), 5.19-5.14 (m, 1H), 4.99 (d, J=2.4 Hz, 1H), 4.97 (t, J=4.0 Hz,2H), 4.91 (d, J=2.6 Hz, 1H), 4.89 (d, J=4.0 Hz, 1H), 4.81-4.78 (m, 1H),4.78-4.75 (m, 1H), 4.74 (d, J=3.6 Hz, 1H), 4.72 (d, J=3.9 Hz, 1H), 4.66(d, J=3.9 Hz, 1H), 4.58 (d, J=10.9 Hz, 1H), 4.48 (bs, 1H), 4.47 (d,J=3.0 Hz, 1H), 4.44-4.42 (m, 1H), 4.42 (d, J=5.4 Hz, 1H), 4.32 (d, J=2.1Hz, 1H), 4.30-4.28 (m, 1H), 4.27 (d, J=2.2 Hz, 1H), 4.25-4.23 (m, 1H),4.23 (d, J=3.6 Hz, 2H), 4.21-4.17 (m, 2H), 4.16 (d, J=2.2 Hz, 1H), 4.14(t, J=6.0 Hz, 2H), 4.07-4.03 (m, 1H), 3.96-3.91 (m, 1H), 3.89 (t, J=7.8Hz, 2H), 3.81 (d, J=3.7 Hz, 1H), 3.79-3.76 (m, 1H), 3.75 (s, 3H), 3.67(d, J=9.6 Hz, 1H), 3.63 (s, 3H), 3.60 (d, J=8.9 Hz, 1H), 3.57 (d, J=9.1Hz, 1H), 3.54 (s, 3H), 3.52 (d, J=9.4 Hz, 1H), 3.49 (d, J=2.8 Hz, 1H),3.47 (d, J=2.6 Hz, 1H), 3.45 (s, 3H), 3.28 (d, J=3.6 Hz, 1H), 3.26 (d,J=3.7 Hz, 1H), 3.25 (t, J=3.5 Hz, 2H), 3.23 (t, J=3.2 Hz, 2H), 2.077 (s,3H), 2.073 (s, 3H), 1.97 (s, 3H); ¹³C-NMR (CDCl₃) δ 170.7, 170.6, 170.5,169.5, 169.4, 169.2, 165.6, 165.2, 155.3, 150.5, 137.9, 137.8, 137.7,137.6, 137.55, 137.5, 137.4, 137.3, 133.6, 133.5, 129.96, 129.9, 129.5,129.2, 129.0, 128.8, 128.7, 128.5, 128.4, 128.2, 128.1, 128.0, 127.9,127.8, 127.5, 125.3, 117.9, 114.7, 99.1, 98.9, 98.6, 98.5, 98.4, 98.2,98.1, 79.9, 78.4, 78.3, 77.5, 77.3, 77.0, 75.9, 75.5, 75.4, 75.0, 74.8,74.7, 74.4, 74.3, 74.1, 72.9, 72.5, 71.5, 69.8, 69.7, 68.1, 63.5, 63.4,63.2, 62.3, 61.7, 55.7, 52.1, 52.0, 51.7, 21.4, 20.8.

Synthesis of 53

Compound 53 is prepared from compound 47 following general procedure G3:179 mg, 75%, R_(f)=0.55 (Toluene/EtOAc 4:1). ¹³C-NMR (125 MHz, CDCl₃) δ170.6, 170.5, 168.1, 167.7, 167.6, 165.0, 164.7, 155.7, 151.0, 138.2,138.1, 137.9, 137.6, 137.5, 137.3, 137.2, 137.1, 133.7, 133.5, 129.95,129.9, 129.8, 129.4, 129.1, 129.0, 128.9, 128.8, 128.6, 128.4, 128.3,128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5, 118.7, 114.5, 101.11,101.1, 100.7, 97.7, 97.3, 97.2, 82.9, 82.6, 82.2, 80.2, 78.0, 77.8,77.6, 77.5, 75.6, 75.3, 75.0, 74.95, 74.9, 74.8, 74.7, 74.5, 74.4, 74.3,74.1, 73.8, 73.6, 73.5, 69.9, 69.15, 69.1, 63.4, 62.8, 62.2, 61.55,61.5, 55.6, 52.7, 52.1, 52.0, 20.9, 20.8

Synthesis of 54

Compound 54 is prepared from compound 48 following general procedure G1:The residue is purified by silica gel chromatography (EtOAc:petroleumether, 2:3) to furnish the disaccharide as a foam, 72 mg, 80% yield,R_(f)=0.5 (EtOAc:petroleum ether, 2:3). HRMS (ESI) calcd forC₁₅₈H₁₆₂N₁₂O₅₀Na(M+Na)⁺ m/z 3050.04, found 3050.0403. ¹H-NMR (500 MHz,CDCl₃) δ 8.14-8.06 (m, 8 H), 7.56-7.48 (m, 4 H), 7.48-7.43 (m, 6 H),7.43-7.39 (m, 10H), 7.38-7.33 (m, 12H), 7.33-7.28 (m, 5 H), 7.28-7.22(m, 6H), 7.22-7.17 (m, 8H), 7.16-7.10 (m, 6H), 7.03 (d, J=8.7 Hz, 2H),6.81 (d, J=9.3 Hz, 2H), 5.71 (d, J=3.9 Hz, 1H), 5.50 (d, J=5.1 Hz, 1H),5.47 (d, J=6.0 Hz, 1H), 5.45 (d, J=6.0 Hz, 1H), 5.31 (t, J=2.4 Hz, 2H),5.19-5.14 (m, 2H), 4.98 (bs, 1H), 4.97-4.94 (m, 3H), 4.92 (d, J=3.9 Hz,1H), 4.90-4.88 (m, 3H), 4.82-4.74 (m, 4H), 4.72-4.67 (m, 2H), 4.66 (d,J=5.2 Hz, 1H), 4.58 (d, J=11.1 Hz, 1H), 4.49-4.46 (m, 2H), 4.45-4.40 (m,2H), 4.36 (d, J=5.9 Hz, 1H), 4.32-4.30 (m, 5H), 4.29-4.21 (m, 3H),4.21-4.15 (m, 4H), 4.15-4.10 (m, 3H), 4.09-4.02 (m, 2H), 3.96-3.92 (m,2H), 3.91 (d, J=6.3 Hz, 1H), 3.88-3.83 (m, 2H), 3.80-3.72 (m, 2H), 3.75(s, 3H), 3.68 (d, J=10.5 Hz, 1H), 3.63 (s, 3H), 3.61 (d, J=9.8 Hz, 1H),3.57 (d, J=5.6 Hz, 1H), 3.53 (s, 3H), 3.52 (d, J=7.0 Hz, 1H), 3.48 (s,3H), 3.47-3.45 (m, 2H), 3.44 (s, 3H), 3.30-3.27 (m, 1H), 3.27 (d, J=2.3Hz, 1H), 3.26-3.24 (m, 2H), 3.24-3.22 (m, 2H), 3.21 (d, J=3.4 Hz, 1H),2.07 (s, 3H), 2.06 (s, 6H), 1.96 (s, 3H); ¹³C-NMR (125 MHz, CDCl₃) δ170.67, 170.6, 170.5, 169.5, 169.4, 169.2, 165.6, 165.2, 155.3, 150.5,137.8, 137.7, 137.6, 137.3, 137.2, 133.7, 133.6, 129.96, 129.9, 129.86,129.5, 129.2, 129.1, 128.8, 128.7, 128.5, 128.47, 128.4, 128.37, 128.3,128.2, 128.1, 127.9, 127.8, 127.9, 127.8, 127.7, 127.6, 127.5, 117.9,114.7, 99.1, 98.9, 98.7, 98.6, 98.3, 98.2, 98.1, 98.0, 79.9, 78.4, 77.5,77.3, 77.1, 76.8, 76.2, 75.9, 75.8, 75.6, 75.1, 75.0, 74.9, 74.7, 74.6,74.3, 74.1, 72.8, 72.5, 71.7. 71.1, 70.9, 70.5, 70.1, 69.8, 69.7, 68.1,63.5, 63.4, 63.2, 63.1, 63.0, 62.3, 61.8, 61.6, 55.7, 52.1, 52.0, 20.7.

Synthesis of 55

Compound 55 is prepared from compound 49 following general procedure G2:426 mg, 59%, R_(f)=0.5 (Toluene/EtOAc 4:1). ¹³C-NMR (125 MHz, CDCl₃) δ170.65, 170.6, 168.1, 167.8, 167.6, 165.1, 164.75, 164.7, 155.8, 151.0,138.2, 138.1, 137.9, 137.7, 137.6, 137.3, 137.2, 137.1, 133.8, 133.5,129.9, 129.8, 129.5, 129.1, 129.0, 128.9, 128.8, 128.6, 128.4, 128.3,128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 118.8, 114.6, 101.2, 100.8,97.7, 97.4, 97.3, 82.9, 82.6, 82.2, 80.3, 77.9, 75.6, 75.3, 75.1, 75.0,74.7, 74.6, 74.5, 74.3, 74.1, 73.8, 73.6, 70.0, 69.2, 63.5, 62.8, 62.3,61.5, 55.6, 52.8, 52.1, 52.0, 20.9

Synthesis of 56

Compound 56 is prepared from compound 50 following general procedure G1:The residue is purified by silica gel chromatography (EtOAc:petroleumether, 2:3) to furnish the disaccharide as a foam, 92 mg, 77% yield,R_(f)=0.45 (EtOAc:petroleum ether, 2:3). HRMS (ESI) calcd forC₁₉₄H₁₉₉N₁₅O₆₂Na(M+Na)⁺ m/z 3753.284, found 3753.281. ¹H-NMR (500 MHz,CDCl₃) δ 8.13-8.07 (m, 10 H), 7.57-7.52 (m, 4 H), 7.52 (d, J=8.3 Hz,1H), 7.49-7.43 (m, 10 H), 7.43-7.39 (m, 8H), 7.38-7.33 (m, 14H),7.33-7.28 (m, 10 H), 7.28-7.23 (m, 12H), 7.22-7.16 (m, 6H), 7.15-7.10(m, 4H), 7.03 (d, J=8.9 Hz, 2H), 6.81 (d, J=9.4 Hz, 2H), 5.71 (d, J=3.9Hz, 1H), 5.50 (t, J=4.4 Hz, 2H), 5.47 (d, J=2.9 Hz, 1H), 5.45 (t, J=5.6Hz, 2H), 5.32 (t, J=3.2 Hz, 2H), 5.20-5.13 (m, 2H), 4.99-4.94 (m, 2H),4.93-4.88 (m, 2H), 4.82-4.79 (m, 4H), 4.79-4.75 (m, 2H), 4.75 (d, J=3.9Hz, 1H), 4.72 (d, J=4.1 Hz, 1H), 4.69-4.67 (m, 4H), 4.67-4.64 (m, 4H),4.58 (d, J=11.1 Hz, 1H), 4.50-4.46 (m, 3 H), 4.45-4.41 (m, 2H), 4.40 (d,J=5.9 Hz, 1H), 4.36 (d, J=5.3 Hz, 1H), 4.32-4.30 (m, 3H), 4.30-4.27 (m,5H), 4.27-4.21 (m, 4H), 4.21-4.15 (m, 2H), 4.15-4.11 (m, 3H), 4.11-4.08(m, 3H), 4.08-4.03 (m, 2H), 3.97-3.90 (m, 2H), 3.89-3.82 (m, 2H),3.80-3.77 (m, 2H), 3.75 (s, 3H), 3.74-3.70 (m, 2H), 3.68-3.65 (m, 2H),3.63 (s, 3H), 3.61 (d, J=9.9 Hz, 1H), 3.57 (d, J=2.0 Hz, 1H), 3.53 (s,3H), 3.51-3.50 (m, 1H), 3.48 (s, 3H), 3.46 (s, 3H), 3.43 (s, 3H), 3.30(t, J=3.5 Hz, 2H), 3.28-3.26 (m, 1H), 3.26 (t, J=3.3 Hz, 2H), 3.24 (d,J=3.6 Hz, 1H), 3.22 (d, J=3.8 Hz, 1H), 2.07 (s, 6H), 2.06 (s, 6H), 1.96(s, 3H); ¹³C-NMR (125 MHz, CDCl₃) δ 170.7, 170.64, 170.6, 170.5, 169.6,169.55, 169.5, 169.2, 165.6, 165.22, 165.2, 165.19, 165.17, 155.3,150.5, 137.8, 137.7, 137.66, 137.6, 137.5, 137.4, 137.3, 137.1, 133.8,133.6, 133.5, 129.9, 129.8, 129.5, 129.2, 129.1, 128.8, 128.7, 128.5,128.49, 128.4, 128.39, 128.37, 128.3, 128.2, 128.15, 128.1, 128.0,127.95, 127.9, 127.8, 127.7, 127.6, 127.5, 117.97, 114.7, 99.1, 98.9,98.8, 98.7, 98.6, 98.4, 98.2, 98.1, 98.03, 98.01, 80.0, 78.4, 78.1,77.7, 76.2, 75.9, 75.8, 75.6, 75.5, 75.1, 75.0, 74.9, 74.7, 74.6, 74.4,74.1, 72.9, 71.8, 71.7, 71.6, 71.3, 71.2, 70.9, 70.6, 70.1, 69.8, 69.7,68.1, 63.2, 61.8, 61.7, 55.7, 52.1, 52.0, 51.8, 20.8.

Synthesis of 140

Compound 140 is prepared from compound 139 following general procedureG1: The residue is purified by silica gel chromatography(EtOAc:petroleum ether, 1:1) to furnish the disaccharide as a foam (325mg, 73.3 μmol, 76% yield); TLC (EtOAc:petroleum ether, 2:3, v/v):R_(f)=0.41; HRMS (ESI) calcd for C₂₃₀H₂₃₆N₁₈O₇₄Na₂ (M+2Na)²⁺ m/z2241.2573, found 2241.2549. ¹H-NMR (500 MHz, CDCl₃) δ 8.14-8.06 (m, 10H), 7.57-7.52 (m, 4 H), 7.52 (d, J=7.3 Hz, 2H), 7.49-7.43 (m, 10 H),7.43-7.40 (m, 8H), 7.37-7.33 (m, 14H), 7.32-7.27 (m, 18 H), 7.26-7.21(m, 14H), 7.21-7.15 (m, 10H), 7.15-7.11 (m, 5H), 7.03 (d, J=9.1 Hz, 2H),6.81 (d, J=9.1 Hz, 2H), 5.72 (d, J=3.8 Hz, 1H), 5.51-5.41 (m, 4H), 5.32(t, J=3.2 Hz, 2H), 5.20-5.14 (m, 3H), 4.99-4.95 (m, 3H), 4.94-4.87 (m,5H), 4.84-4.73 (m, 6H), 4.72-4.68 (m, 8H), 4.67-4.64 (m, 4H), 4.58 (d,J=10.8 Hz, 1H), 4.50-4.41 (m, 5H), 4.40-4.37 (m, 6H), 4.36 (d, J=5.0 Hz,1H), 4.33-4.28 (m, 7H), 4.27-4.16 (m, 6H), 4.16-4.12 (m, 4H), 4.11-4.09(m, 4H), 4.08-4.03 (m, 3H), 3.97-3.90 (m, 5H), 3.89-3.82 (m, 4H),3.81-3.75 (m, 3H), 3.74 (s, 3H), 3.68-3.65 (m, 2H), 3.64 (s, 3H),3.62-3.54 (m, 4H), 3.53 (s, 3H), 3.51-3.50 (m, 1H), 3.49 (s, 3H), 3.47(s, 3H), 3.46 (s, 3H), 3.43 (s, 3H), 3.31-3.27 (m, 3H), 3.26-3.24 (m,2H), 3.24 (d, J=3.4 Hz, 1H), 3.22 (d, J=3.6 Hz, 1H), 2.07 (s, 9H), 2.06(s, 6H), 1.96 (s, 3H); ¹³C-NMR (125 MHz, CDCl₃) δ 170.7, 170.6, 170.5,169.6, 169.5, 169.2, 165.6, 165.2, 155.3, 150.5, 137.8, 137.7, 137.6,137.5, 137.4, 137.3, 133.8, 133.6, 133.5, 129.9, 129.5, 129.2, 129.1,128.8, 128.7, 128.5, 128.4, 128.3, 128.2, 128.1, 128.05, 128.01, 127.9,127.8, 127.7, 127.6, 127.5, 117.9, 114.6, 99.1, 98.9, 98.7, 98.4, 98.2,98.0, 80.0, 78.4, 78.1, 76.9, 76.3, 76.2, 76.1, 75.9, 75.8, 75.6, 75.5,75.0, 74.9, 74.7, 74.4, 74.1, 72.8, 72.5, 71.8, 71.7, 71.6, 71.3, 71.2,71.1, 70.9, 70.5, 70.1, 69.8, 69.7, 68.1, 66.6, 66.5, 63.5, 63.4, 63.2,63.0, 62.3, 61.7, 61.6, 60.4, 55.7, 52.1, 52.0, 51.8, 20.8.

Synthesis of 57

Compound 57 is prepared from compound 51 following general procedure G2:426 mg, 51%, R_(f)=0.46 (Toluene/EtOAc 4:1). ¹³C-NMR (125 MHz, CDCl₃) δ170.6, 170.5, 168.0, 167.7, 167.5, 165.0, 164.65, 164.6, 155.7, 150.9,138.1, 138.05, 138.0, 137.6, 137.5, 137.2, 137.1, 137.0, 133.7, 133.5,129.9, 129.8, 129.4, 129.3, 129.0, 128.9, 128.8, 128.3, 128.2, 128.1,127.9, 127.8, 127.7, 127.6, 118.7, 114.5, 101.1, 100.7, 97.7, 97.2,97.1, 82.9, 82.6, 82.2, 80.2, 77.8, 75.6, 75.3, 75.0, 74.9, 74.8, 74.7,74.6, 74.5, 74.4, 74.2, 74.0, 73.7, 73.5, 69.8, 69.0, 62.7, 61.5, 61.4,61.3, 55.6, 52.7, 52.0, 51.9, 20.8

General Procedure H (GPH): Reduction of Azide Group.

Thiolacetic acid (1 mL for 20 μmol) is added to the starting material indry pyridine (1 mL for 20 μmol) at at room temperature. The reactionmixture is stirred at room temperature for 48-72 hours. After TLC(EtOAc:Toluene, 4:1) indicates the completion of the reaction toluene isadded and the solution is washed with water, diluted HCl and NaHCO₃solution (sat., aq.), dried and concentrated. Chromatography(EtOAc:Toluene, 4:1) affords N-acetylated products.

Synthesis of 58

Compound 58 is prepared from compound 52 following general procedure H:The residue is purified by silica gel chromatography (Toluene:EtOAc,1:4) to furnish the disaccharide as a foam, 215 mg, 83% yield, Rf=0.68(EtOAc:petroleum ether, 4:1). HRMS (ESI) calcd for C₁₂₈H₁₃₇N₃O₄₁Na(M+Na)⁺ m/z 2394.8625, found 2394.8635. ¹H-NMR (500 MHz, CDCl₃)7.95-7.90 (m, 6 H), 7.49-7.42 (m, 6 H), 7.39-7.31 (m, 12H), 7.28-7.20(m, 10 H), 7.20-7.12 (m, 10H), 7.10-7.06 (m, 6H), 6.95 (d, J=9.3 Hz,2H), 6.73 (d, J=8.8 Hz, 2H), 5.78 (d, J=9.1 Hz, 1H), 5.70 (d, J=9.1 Hz,1H), 5.59 (d, J=3.5 Hz, 1H), 5.28-5.25 (m, 1H), 5.24 (d, J=4.9 Hz, 1H),5.16 (d, J=9.1 Hz, 1H), 5.12 (t, J=4.2 Hz, 2H), 5.10 (t, J=4.2 Hz, 2H),4.89-4.85 (m, 1H), 4.84 (d, J=3.6 Hz, 1H), 4.80 (d, J=11.5 Hz, 1H), 4.74(d, J=4.7 Hz, 1H), 4.71-4.69 (m, 1H), 4.68 (d, J=10.5 Hz, 1H), 4.63 (d,J=10.0 Hz, 1H), 4.59 (d, J=3.6 Hz, 1H), 4.55 (d, J=11.5 Hz, 1H), 4.50(d, J=11.0 Hz, 1H), 4.38 (t, J=11.0 Hz, 2H), 4.31-4.28 (m, 1H),4.26-4.20 (m, 1H), 4.19 (d, J=4.3 Hz, 1H), 4.17-4.15 (m, 1H), 4.14-4.11(m, 1H), 4.11-4.08 (m, 2H), 4.07-4.04 (m, 1H), 4.03 (m, 1H), 4.02 (t,J=3.4 Hz, 2H), 4.0 (d, J=4.6 Hz, 1H), 3.97 (d, J=4.8 Hz, 1H), 3.95 (t,J=3.5 Hz, 2H), 3.93 (t, J=4.2 Hz, 2H), 3.90-3.84 (m, 1H), 3.73 (t, J=2.3Hz, 2H), 3.71 (t, J=3.1 Hz, 2H), 3.67 (s, 3H), 3.66-3.64 (m, 1H),3.60-3.58 (m, 1H), 3.58-3.54 (m, 1H), 3.54-3.53 (m, 1H), 3.51 (s, 6H),3.43-3.37 (m, 1H), 3.37-3.30 (m, 1H), 3.29 (s, 3H), 2.02 (s, 6H), 2.01(s, 3H), 1.42 (s, 3H), 1.32 (s, 3H), 1.24 (s, 3H); ¹³C-NMR (125 MHz,CDCl₃) δ 171.1, 170.9, 170.6, 170.2, 170.1, 169.9, 169.2, 169.0, 165.6,165.4, 155.4, 150.42, 138.4, 138.3, 138.0, 137.8, 137.0, 136.8, 133.9,133.8, 129.7, 129.0, 128.9, 128.6, 128.56, 128.5, 128.46, 128.2, 128.1,128.0, 127.9, 127.7, 127.6, 127.4, 127.2, 118.1, 114.7, 98.4, 98.3,98.25, 98.2, 98.1, 98.0, 97.9, 80.5, 78.2, 78.1, 77.3, 77.0, 75.2, 75.1,74.96, 74.9, 74.7, 74.2, 73.9, 73.7, 73.6, 73.2, 72.9, 72.8, 72.7, 72.5,71.5, 71.3, 70.5, 70.4, 70.3, 70.2, 70.1, 68.7, 62.4, 61.7, 61.6, 55.6,52.4, 52.1, 52.0, 51.9, 51.7, 22.9, 22.7, 22.6, 21.0, 20.9, 20.7.

Synthesis of 59

Compound 59 is prepared from compound 53 following general procedure H:124 mg, 75%; ¹³C-NMR (125 MHz, CDCl₃) δ 170.7, 170.6, 170.1, 167.6,167.4, 155.7, 150.8, 138.7, 138.1, 137.7, 136.5, 136.4, 136.3, 133.8,133.6, 129.8, 129.2, 129.0, 128.8, 128.6, 128.55, 128.5, 128.45, 128.3,128.2, 128.15, 128.1, 128.0, 127.9, 127.8, 127.5, 127.4, 127.3, 118.6,114.5, 101.2, 101.1, 100.9, 99.5, 99.0, 98.7, 81.6, 81.4, 80.8, 80.5,78.0, 77.9, 77.8, 75.4, 75.25, 75.2, 75.15, 75.0, 74.95, 74.85, 74.8,74.4, 74.3, 73.9, 73.7, 73.6, 70.7, 70.2, 70.1, 62.2, 61.5, 61.4, 55.6,52.8, 52.6, 52.5, 52.1, 52.0, 22.65, 22.6, 20.8, 20.77, 20.7

Synthesis of 60

Compound 60 is prepared from compound 54 following general procedure H:The residue is purified by silica gel chromatography (Toluene:EtOAc,1:4) to furnish the disaccharide as a foam, 36 mg, 70% yield, R_(f)=0.5(EtOAc:Toluene, 4:1). HRMS (ESI) calcd for C₁₆₆H₁₇₈N₄O₅₄Na (M+Na)⁺ m/z3114.1203, found 3114.1204. ¹H-NMR (500 MHz, CDCl₃) 8.02 (d, J=10.1 Hz,6H), 7.57-7.50 (m, 6 H), 7.47-7.39 (m, 6 H), 7.36-7.27 (m, 12H),7.27-7.24 (m, 10 H), 7.24-7.18 (m, 10H), 7.18-7.14 (m, 6H), 7.13-7.10(m, 6H), 7.01 (d, J=9.2 Hz, 2H), 6.80 (d, J=9.2 Hz, 2H), 5.81 (d, J=9.5Hz, 1H), 5.78 (d, J=9.3 Hz, 1H), 5.75 (d, J=9.4 Hz, 1H), 5.66 (d, J=2.0Hz, 1H), 5.36-5.32 (m, 1H), 5.31 (t, J=5.1 Hz, 2H), 5.21-5.15 (m, 2H),4.95-4.92 (m, 1H), 4.92 (t, J=3.5 Hz, 2H), 4.88 (d, J=11.5 Hz, 1H), 4.81(d, J=3.8 Hz, 1H), 4.79 (t, J=4.3 Hz, 2H), 4.75 (d, J=4.5 Hz, 1H),4.73-4.69 (m, 3H), 4.69 (d, J=2.1 Hz, 1H), 4.66 (bs, 1H), 4.64-4.61 (m,3H), 4.61-4.58 (m, 2H), 4.58 (d, J=4.1 Hz, 1H), 4.55 (d, J=3.6 Hz, 1H),4.46 (d, J=11.0 Hz, 1H), 4.41 (d, J=11.5 Hz, 1H), 4.36-4.34 (m, 4H),4.33-4.25 (m, 4H), 4.23-4.21 (m, 5H), 4.21-4.19 (m, 2H), 4.19-4.17 (m,2H), 4.17-4.13 (m, 2H), 4.13 (d, J=11.5 Hz, 1H), 4.09-4.05 (m, 1H), 4.05(d, J=4.7 Hz, 1H), 4.02-4.0 (m, 1H), 4.0-3.95 (m, 1H), 3.81-3.79 (m,1H), 3.79-3.76 (m, 1H), 3.75 (s, 3H), 3.74-3.70 (m, 1H), 3.67-3.61 (m,1H), 3.59 (s, 3H), 3.57 (s, 3H), 3.50 (d, J=10.1 Hz, 1H), 3.47 (d, J=3.8Hz, 1H), 3.44 (d, J=2.4 Hz, 1H), 3.42-3.39 (m, 1H), 3.39-3.37 (m, 1H),3.35 (s, 3H), 3.34 (s, 3H), 2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H),1.98 (s, 3H), 1.49 (s, 3H), 1.389 (s, 3H), 1.384 (s, 3H), 1.31 (s, 3H);¹³C-NMR (CDCl₃) δ 170.9, 170.6, 170.1, 169.9, 169.2, 165.6, 165.4,155.4, 150.4, 138.4, 138.0, 137.8, 137.0, 136.8, 136.4, 133.8, 129.8,129.0, 128.9, 128.6, 128.5, 128.4, 128.3, 128.2, 128.15, 128.1, 128.0,127.7, 127.6, 127.4, 127.2, 126.9, 118.0, 114.7, 98.4, 98.37, 98.3,98.2, 98.15, 98.1, 97.95, 97.9, 80.5, 78.1, 77.3, 77.0, 76.8, 75.4,75.2, 75.1, 74.96, 74.9, 74.7, 73.7, 73.2, 72.9, 72.8, 72.5, 71.6, 71.4,70.5, 70.4, 70.2, 68.7, 68.3, 62.4, 61.5, 61.6, 55.7, 52.6, 52.4, 52.37,52.3, 52.0, 51.7, 29.7, 29.3, 20.9, 20.7.

Synthesis of 61

Compound 61 is prepared from compound 55 following general procedure H:316 mg, 75%. ¹³C-NMR (125 MHz, CDCl₃) δ 170.7, 170.65, 170.6, 170.2,170.1, 167.7, 167.5, 167.4, 167.3, 165.0, 164.9, 164.8, 155,7, 150.9,138.8, 138.7, 138.1, 137.9, 137.7, 136.5, 136.4, 136.35, 136.3, 133.9,133.6, 129.8, 129.75, 129.2, 129.1, 128.9, 128.8, 128.65, 128.6, 128.55,128.55, 128.5, 128. 4, 128.3, 128.25, 128.2, 128.1, 128.05, 128.0,127.95, 127.85, 127.8, 127.55, 127.5, 127.45, 127.4, 127.35, 118.6,114.5, 101.1, 100.9, 99.5, 99.0, 98.7, 98.6, 81.6, 81.4, 80.9, 80.5,78.0, 77.9, 77.8, 76.7, 76.6, 75.4, 75.2, 75.1, 75.0, 74.95, 74.9, 74.8,74.5, 74.45, 74.4, 73.8, 73.65, 73.6, 73.55, 70.7, 70.2, 70.1, 62.2,61.5, 61.4, 55.6, 52.8, 52.7, 52.5, 52.1, 52.0, 22.7, 22.65, 22.65,22.6, 21.5, 20.8, 20.75, 20.7

Synthesis of 62

Compound 62 is prepared from compound 56 following general procedure H:The residue is purified by silica gel chromatography (Toluene:EtOAc,1:4) to furnish the disaccharide as a foam, 69 mg, 90% yield, Rf=0.5(EtOAc:Toluene, 4:1). HRMS (ESI) calcd for C₂₀₄H₂₁₉N₅O₆₇Na (M+Na)⁺ m/z3833.398, found 3833.397. ¹H-NMR (500 MHz, CDCl₃) 8.02-7.98 (m, 8H),7.57-7.50 (m, 6 H), 7.47-7.39 (m, 8 H), 7.36-7.28 (m, 14H), 7.27-7.23(m, 18 H), 7.23-7.14 (m, 16H), 7.13-7.09 (m, 10H), 7.01 (d, J=8.8 Hz,2H), 6.81 (d, J=9.1 Hz, 2H), 5.84-5.79 (m, 1H), 5.79 (d, J=10.3 Hz, 1H),5.66 (d, J=3.4 Hz, 1H), 5.40-5.35 (m, 1H), 5.35-5.32 (m, 1H), 5.30-5.26(m, 2H), 5.24 (d, J=8.5 Hz, 1H), 5.18-5.13 (m, 2H), 4.95-4.93 (m, 1H),4.92-4.89 (m, 2H), 4.87 (d, J=11.4 Hz, 1H), 4.81 (d, J=4.0 Hz, 1H),4.79-4.76 (m, 4H), 4.75-4.72 (m, 4H), 4.72-4.70 (m, 4H), 4.69-4.67 (m,3H), 4.67-4.65 (m, 4H), 4.64-4.61 (m, 3H), 4.60-4.58 (m, 4H), 4.58-4.56(m, 2H), 4.55 (d, J=3.6 Hz, 1H), 4.46-4.39 (m, 1H), 4.38-4.34 (m, 3H),4.33-4.27 (m, 3H), 4.27 (d, J=4.2 Hz, 1H), 4.23-4.21 (m, 3H), 4.21-4.19(m, 2H), 4.18-4.14 (m, 2H), 4.13-4.11 (m, 2H), 4.10-4.06 (m, 1H), 4.05(d, J=5.1 Hz, 1H), 4.03-4.0 (m, 3H), 4.0-3.96 (m, 4H), 3.95-3.91 (m,1H), 3.80-3.78 (m, 1H), 3.78-3.76 (m, 1H), 3.75 (s, 3H), 3.74-3.73 (m,1H), 3.72-3.70 (m, 1H), 3.66-3.60 (m, 2H), 3.58 (s, 3H), 3.57 (s, 3H),3.50-3.47 (m, 2H), 3.46-3.42 (m, 1H), 3.42-3.38 (m, 1H), 3.36 (s, 3H),3.34 (s, 3H), 3.33 (s, 3H), 3.28 (d, J=6.0 Hz, 1H), 2.09 (s, 3H), 2.08(s, 3H), 2.07 (s, 6H), 1.98 (s, 3H), 1.49 (s, 3H), 1.38 (s, 6H), 1.37(s, 3H), 1.31 (s, 3H); ¹³C-NMR (CDCl₃) δ 171.1, 170.9, 170.6, 170.2,169.9, 169.2, 169.0, 165.6, 165.4, 165.3, 155.4, 150.4, 138.4, 138.0,137.8, 137.1, 136.8, 136.4, 133.9, 130.9, 129.7, 129.1, 129.0, 128.9,128.6, 128.5, 128.2, 128.1, 128.0, 127.7, 127.4, 127.2, 127.1, 127.06,127.0, 118.1, 114.7, 98.4, 98.33, 98.3, 98.25, 98.2, 98.1, 97.96, 97.9,97.75, 97.7, 80.5, 78.2, 78.1, 77.3, 77.1, 75.2, 75.1, 74.98, 74.9,74.7, 74.1, 73.7, 73.6, 72.9, 72.8, 72.6, 71.7, 71.5, 71.3, 70.5, 70.4,70.2, 68.7, 68.3, 64.7, 62.5, 61.6, 55.7, 52.4, 52.1, 51.9, 51.7, 22.9,22.7, 20.9, 20.8.

Synthesis of 141

Compound 141 is prepared from compound 140 following general procedureH: The residue is purified by silica gel chromatography (Toluene:EtOAc,1:4) to furnish the disaccharide as a clear syrup, 212 mg, 46.8 μmol,92% yield; TLC (Toluene:EtOAc, 1:4, v/v): R_(f)=0.45; HRMS (ESI) calcdfor C₂₄₂H₂₆₀N₆O₆₀Na₂ (M+2Na)²⁺ m/z 2288.8162, found 2288.8108; ¹H-NMR(500 MHz, CDCl₃) 8.03-7.97 (m, 8H), 7.58-7.50 (m, 4 H), 7.48-7.39 (m, 5H), 7.36-7.28 (m, 14H), 7.28-7.22 (m, 28 H), 7.22-7.14 (m, 22H),7.14-7.1 (m, 12H), 7.02 (d, J=9.1 Hz, 2H), 6.81 (d, J=9.1 Hz, 2H),5.88-5.79 (m, 3H), 5.67 (d, J=2.1 Hz, 1H), 5.35-5.32 (m, 2H), 5.32-5.25(m, 3H), 5.19-5.13 (m, 3H), 4.97-4.94 (m, 1H), 4.93-4.89 (m, 2H), 4.88(d, J=11.9 Hz, 1H), 4.82-4.76 (m, 6H), 4.75-4.70 (m, 10H), 4.70-4.68 (m,8H), 4.68-4.62 (m, 12H), 4.61-4.58 (m, 3H), 4.58-4.54 (m, 3H), 4.47-4.43(m, 3H), 4.43-4.35 (m, 4H), 4.34-4.25 (m, 5H), 4.25-4.23 (m, 1H),4.22-4.19 (m, 2H), 4.19-4.15 (m, 3H), 4.15-4.12 (m, 1H), 4.11-4.06 (m,2H), 4.06 (d, J=5.5 Hz, 1H), 4.04-4.01 (m, 2H), 4.0-3.91 (m, 5H),3.81-3.77 (m, 2H), 3.74 (s, 3H), 3.68-3.60 (m, 4H), 3.59 (s, 3H), 3.58(s, 3H), 3.51-3.49 (m, 1H), 3.49 (d, J=2.2 Hz, 1H), 3.47-3.45 (m, 1H),3.45-3.43 (m, 1H), 3.43-3.38 (m, 2H), 3.37 (s, 3H), 3.35 (s, 3H), 3.34(s, 3H), 3.33 (s, 3H), 2.1 (s, 3H), 2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s,6H), 1.98 (s, 3H), 1.49 (s, 3H), 1.39 (s, 3H), 1.38 (s, 6H), 1.37 (s,3H), 1.31 (s, 3H); ¹³C-NMR (125 MHz, CDCl₃) δ 171.0, 170.6, 170.2,169.9, 169.2, 169.0, 165.6, 165.4, 155.4, 150.4, 138.4, 138.0, 137.8,137.0, 136.8, 133.9, 130.8, 129.7, 128.9, 128.6, 128.5, 128.2, 128.0,127.7, 127.6, 127.4, 127.2, 127.1, 127.0, 125.3, 118.1, 114.7, 98.3,98.1, 97.9, 97.8, 80.5, 78.2, 76.9, 75.1, 74.9, 74.8, 74.6, 74.1, 73.7,73.5, 73.2, 72.9, 72.7, 72.6, 72.5, 71.6, 71.5, 70.5, 70.4, 70.2, 68.7,68.3, 68.2, 62.4, 61.6, 60.4, 55.6, 52.4, 52.1, 52.0, 51.8, 51.7, 22.9,22.7, 21.5, 20.9, 20.7.

Synthesis of 63

Compound 63 is prepared from compound 57 following general procedure H:280 mg, 78%. ¹³C-NMR (125 MHz, CDCl₃) δ 170.7, 170.6, 170.2, 167.7,167.4, 167.35, 167.3, 165.0, 164.9, 164.8, 155.7, 150.9, 138.8, 138.1,137.9, 137.7, 136.5, 136.4, 136.3, 133.9, 133.6, 129.8, 129.2, 129.1,128.8, 128.7, 128.6, 128.35, 128.3, 128.2, 128.1, 128.0, 127.8, 127.5,127.4, 118.6, 114.5, 101.2, 100.9, 99.6, 99.0, 98.75, 98.7, 81.6, 81.4,80.8, 80.6, 78.1, 77.8, 77.6, 75.4, 75.3, 75.0, 74.9, 74.8, 74.5, 74.45,74.4, 73.9, 73.6, 70.7, 70.2, 70.1, 62.2, 61.5, 61.4, 60.4, 55.6, 53.5,52.9, 52.7, 52.5, 52.1, 52.0, 22.7, 21.5, 20.8

General Procedure I (GPI): Selective De-O-Acetylation.

Starting material is dissolved in dry dichloromethane (2 mL for 9 μmol)at 0° C. and treated with a solution of cold dry methanol (4 mL)containing 80 μL of acetyl chloride. Stirring of the reaction mixture iscontinued for 30 min at 0° and then at 23° C. for 48 h. After TLC(EtOAc) indicates the completion of the reaction dichloromethane isadded and the solution is washed with water and NaHCO₃ solution (sat.,aq.), dried and concentrated. The residues are purified by silica gelchromatography (EtOAc:MeOH, 9:1) to give de-O-acetylated products.

Synthesis of 64

Compound 64 is prepared from compound 58 following general procedure I:152 mg, 80% yield, Rf=0.45 (EtOAc). HRMS (ESI) calcd for C₁₂₂H₁₃₁N₃O₃₈Na(M+Na)⁺ m/z 2268.8308, found 2268.8289. ¹H-NMR (500 MHz, CDCl₃) 7.94 (d,J=7.9 Hz, 2H), 7.89 (t, J=5.4 Hz, 4H), 7.48-7.42 (m, 4 H), 7.42-7.38 (m,6H), 7.37-7.33 (m, 6H), 7.31-7.27 (m, 6H), 7.27-7.22 (m, 8 H), 7.21-7.13(m, 4H), 7.13-7.07 (m, 4H), 7.07-7.02 (m, 4H), 6.95 (d, J=6.9 Hz, 2H),6.92 (d, J=9.2 Hz, 2H), 6.71 (d, J=9.0 Hz, 2H), 5.72 (d, J=8.2 Hz, 1H),5.61 (d, J=9.3 Hz, 1H), 5.57 (d, J=2.2 Hz, 1H), 5.35-5.32 (m, 1H), 5.30(t, J=2.9 Hz, 2H), 5.17 (t, J=3.8 Hz, 2H), 5.12-5.07 (m, 2H), 4.91 (d,J=3.6 Hz, 1H), 4.87-4.85 (m, 2H), 4.84 (d, J=3.3 Hz, 1H), 4.78 (d, J=3.3Hz, 1H), 4.75-4.74 (m, 3H), 4.73-4.71 (m, 4H), 4.70-4.67 (m, 2H),4.67-4.65 (m, 2H), 4.65 (d, J=2.9 Hz, 1H), 4.62 (d, J=11.5 Hz, 1H), 4.58(d, J=5.0 Hz, 1H), 4.55-4.53 (m, 1H), 4.53-4.51 (m, 1H), 4.34 (q, J=11.8Hz, 2H), 4.22-4.17 (m, 1H), 4.15-4.10 (m, 2H), 4.09 (d, J=11.8 Hz, 1H),4.05-4.02 (m, 1H), 4.02-3.97 (m, 2H), 3.95 (t, J=4.1 Hz, 2H), 3.91 (d,J=3.7 Hz, 1H), 3.86 (t, J=3.9 Hz, 2H), 3.72-3.67 (m, 1H), 3.65 (s, 3H),3.63-3.58 (m, 1H), 3.57-3.54 (m, 1H), 3.54-3.51 (m, 1H), 3.50 (s, 3H),3.47 (s, 3H), 3.44-3.40 (m, 1H), 3.40-3.38 (m, 1H), 3.38 (d, J=6.5 Hz,1H), 3.35-3.31 (m, 1H), 3.30 (s, 3H), 1.44 (s, 3H), 1.39 (s, 3H), 1.25(s, 3H); ¹³C-NMR (125 MHz, CDCl₃) δ 170.3, 169.9, 169.2, 169.1, 165.5,165.4, 155.4, 150.5, 138.5, 138.4, 138.2, 138.1, 137.1, 136.9, 133.9,133.8, 133.7, 129.8, 129.7, 129.6, 129.1, 129.0, 128.9, 128.6, 128.5,128.4, 128.2, 128.1, 127.9, 127.89, 127.87, 127.82, 127.8, 127.7, 127.5,127.2, 118.1, 114.7, 98.6, 98.2, 97.9, 97.8, 97.1, 96.9, 79.9, 77.7,77.6, 77.4, 77.1, 74.9, 74.4, 74.2, 74.1, 73.3, 73.2, 73.0, 72.9, 72.8,72.7, 72.6, 72.5, 72.4, 72.3, 72.2, 71.3, 70.9, 70.4, 69.8, 68.8, 61.5,60.7, 60.5, 55.6, 52.6, 52.4, 52.2, 51.8, 29.6, 22.9, 22.7, 22.6.

Synthesis of 65

Compound 65 is prepared from compound 59 following general procedure I:92 mg, 90%, R_(f)=0.35 (dichloromethane/methanol 19:1). ¹³C-NMR (125MHz, CDCl₃) δ 170.15, 170.1, 170.0, 168.0, 167.9, 165.0, 164.95, 164.9,155.7, 150.8, 139.0, 138.9, 138.3, 137.9, 136.5, 133.9, 133.8, 133.5,130.9, 129.7, 129.6, 129.55, 129.3, 129.1, 128.9, 128.6, 128.5, 128.4,128.3, 128.2, 128.15, 128.1, 128.0, 127.9, 127.8, 127.4, 127.3, 127.1,118.6, 114.5, 100.9, 100.6, 100.5, 99.0, 98.6, 98.3, 81.4, 81.3, 81.0,80.1, 77.8, 75.5, 75.2, 75.1, 75.0, 74.95, 74.8, 74.7, 74.2, 73.9, 73.8,73.7, 73.3, 72.6, 72.2, 61.6, 60.1, 55.6, 52.8, 52.65, 52.6, 52.3, 52.2,52.1, 22.7, 22.65

Synthesis of 66

Compound 66 is prepared from compound 60 following general procedure I:21 mg, 93% yield, R_(f)=0.15 (EtOAc:petroleum ether, 4:1). HRMS (ESI)calcd for C₁₅₈H₁₇₀N₄O₅₀Na (M+Na)⁺ m/z 2946.0781, found 2946.0757. ¹H-NMR(500 MHz, CDCl₃) 8.03 (d, J=7.6 Hz, 2H), 7.98-7.93 (m, 4H), 7.57-7.49(m, 4 H), 7.47-7.41 (m, 6H), 7.40-7.37 (m, 8H), 7.36-7.30 (m, 12H),7.30-7.20 (m, 16H), 7.19-7.15 (m, 8H), 7.14-7.11 (m, 5H), 7.02 (d, J=9.0Hz, 2H), 6.81 (d, J=8.6 Hz, 2H), 5.72 (d, J=3.9 Hz, 2H), 5.70 (d, J=3.9Hz, 2H), 5.65 (d, J=2.1 Hz, 1H), 5.62 (d, J=9.5 Hz, 1H), 5.41-5.38 (m,1H), 5.38-5.34 (m, 1H), 5.23 (t, J=4.8 Hz, 2H), 5.20-5.16 (m, 2H), 5.16(d, J=8.6 Hz, 2H), 4.98 (d, J=3.7 Hz, 1H), 4.95 (d, J=3.1 Hz, 1H), 4.93(d, J=3.1 Hz, 1H), 4.86-4.83 (m, 2H), 4.81 (t, J=7.1 Hz, 2H), 4.77 (t,J=2.4 Hz, 2H), 4.74 (d, J=2.7 Hz, 1H), 4.72 (d, J=11.7 Hz, 1H), 4.68 (d,J=6.8 Hz, 1H), 4.65-4.62 (m, 6H), 4.62-4.60 (m, 6H), 4.60-4.59 (m, 4H),4.58-4.56 (m, 4H), 4.40 (t, J=11.8 Hz, 2H), 4.29 (d, J=3.6 Hz, 1H), 4.27(d, J=2.8 Hz, 1H), 4.25 (d, J=3.5 Hz, 1H), 4.22-4.21 (m, 1H), 4.21 (d,J=3.8 Hz, 2H), 4.18 (d, J=3.4 Hz, 1H), 4.16 (d, J=11.8 Hz, 1H),4.09-4.03 (m, 2H), 4.01-3.95 (m, 1H), 3.93-3.89 (m, 1H), 3.75 (s, 3H),3.70-3.65 (m, 1H), 3.65-3.61 (m, 1H), 3.59 (s, 3H), 3.57 (s, 3H),3.56-3.53 (m, 1H), 3.52-3.50 (m, 2H), 3.49-3.45 (m, 1H), 3.44-3.42 (m,1H), 3.44-3.38 (m, 1H), 3.37 (s, 3H), 3.36 (s, 3H), 3.35-3.32 (m, 1H),1.46 (s, 3H), 1.44 (s, 3H), 1.33 (s, 3H), 1.26 (s, 3H); ¹³C-NMR (CDCl₃)δ 170.2, 169.1, 155.4, 138.5, 138.1, 137.0, 136.8, 133.8, 129.7, 129.6,129.0, 128.6, 128.2, 127.9, 127.5, 127.2, 125.3, 118.1, 114.7, 98.15,98.0, 97.9, 97.8, 97.7, 97.4, 97.3, 97.2, 79.8, 77.3, 77.0, 76.8, 74.9,74.7, 74.6, 73.2, 72.9, 72.8, 72.6, 72.5, 72.45, 72.4, 70.4, 69.9, 68.6,68.4, 61.6, 60.6, 52.4, 52.2, 51.8, 29.7, 22.9, 22.7.

Synthesis of 67

Compound 67 is prepared from compound 61 following general procedure I:101 mg, 80%, R_(f)=0.33 (dichloromethane/methanol 19:1). ¹³C-NMR (125MHz, CDCl₃) δ 170.2, 170.15, 170.1, 167.95, 167.9, 165.1, 165.0, 164.9,155.7, 150.8, 139.0, 138.9, 138.3, 137.9, 137.2, 136.5, 133.9, 133.8,133.5, 129.7, 129.6, 129.5, 129.2, 129.1, 128.8, 128.6, 128.5, 128.3,128.25, 128.2, 128.15, 128.1, 128.0, 127.9, 127.8, 127.4, 127.35, 127.3,118.6, 114.5, 100.8, 100.6, 100.5, 100.4, 99.0, 98.6, 98.3, 98.2, 81.4,81.3, 81.2, 81.0, 80.1, 77.8, 76.4, 76.3, 75.5, 75.15, 75.1, 75.05,75.0, 74.95, 74.8, 74.75, 74.7, 74.2, 74.1, 73.9, 73.8, 73.3, 72.6,72.4, 72.3, 61.6, 60.1, 60.0, 55.6, 52.8, 52.65, 52.6, 52.3, 52.15,52.1, 22.65, 22.6

Synthesis of 68

Compound 68 is prepared from compound 62 following general procedure I:27 mg, 87% yield, Rf=0.41 (EtOAc). HRMS (ESI) calcd for C₁₉₄H₂₀₉N₅O₆₂Na(M+Na)⁺ m/z 3623.33, found 3623.2315. ¹H-NMR (500 MHz, CDCl₃) 8.03-8.0(m, 2H), 7.97-7.92 (m, 6H), 7.58-7.52 (m, 4 H), 7.52-7.48 (m, 6H),7.47-7.41 (m, 8H), 7.40-7.35 (m, 12H), 7.35-7.30 (m, 12H), 7.30-7.21 (m,16H), 7.21-7.18 (m, 4H), 7.17-7.14 (m, 8H), 7.14-7.10 (m, 5H), 7.01 (d,J=9.2 Hz, 2H), 6.80 (d, J=9.2 Hz, 2H), 5.75-5.69 (m, 2H), 5.68-5.60 (m,2H), 5.42-5.37 (m, 2H), 5.37-5.34 (m, 2H), 5.23-5.13 (m, 2H), 4.98 (d,J=3.5 Hz, 1H), 4.95 (d, J=3.0 Hz, 1H), 4.93-4.90 (m, 2H), 4.87-4.82 (m,2H), 4.81 (d, J=11.1 Hz, 1H), 4.78 (t, J=3.9 Hz, 2H), 4.74 (d, J=2.7 Hz,1H), 4.72-4.70 (m, 6H), 4.70-4.67 (m, 6H), 4.67 (d, J=6.8 Hz, 1H),4.64-4.62 (m, 4H), 4.62-4.60 (m, 4H), 4.60 (d, J=4.3 Hz, 1H), 4.58 (d,J=4.3 Hz, 1H), 4.41-4.33 (m, 4H), 4.29-4.21 (m, 6H), 4.21 (d, J=4.6 Hz,1H), 4.19 (d, J=4.6 Hz, 1H), 4.16 (d, J=11.2 Hz, 2H), 4.12-4.09 (m, 2H),4.09-4.02 (m, 4H), 4.01-3.95 (m, 2H), 3.95-3.89 (m, 1H), 3.75 (s, 3H),3.72-3.65 (m, 1H), 3.65-3.60 (m, 1H), 3.59 (s, 3H), 3.57 (s, 3H),3.50-3.44 (m, 1H), 3.44-3.39 (m, 1H), 3.37 (s, 3H), 3.35 (s, 3H), 3.34(s, 3H), 1.46 (s, 3H), 1.45 (s, 3H), 1.43 (s, 3H), 1.33 (s, 3H), 1.25(s, 3H); ¹³C-NMR (CDCl₃) δ 170.3, 169.9, 169.2, 169.1, 165.5, 165.4,155.4, 138.5, 138.2, 138.1, 137.1, 136.8, 133.9, 129.8, 129.6, 129.0,128.6, 128.5, 128.2, 127.9, 127.5, 127.4, 127.2, 118.1, 114.7, 98.6,98.5, 98.3, 98.2, 98.1, 97.8, 97.7, 97.1, 97.0, 79.9, 77.6, 77.3, 77.0,76.8, 74.9, 74.8, 74.6, 73.4, 72.9, 72.6, 72.5, 72.4, 72.3, 70.9, 70.2,68.7, 68.4, 60.6, 55.7, 52.6, 52.1, 51.8, 29.7, 22.9, 22.7.

Synthesis of 142

Compound 142 is prepared from compound 141 following general procedureI: 142 mg, 33.2 μmol, 100% yield, TLC (EtOAc): R_(f)=0.38; HRMS (ESI)calcd for C₂₃₀H₂₄₈N₆O₇₄Na₂ (M+2Na)²⁺ m/z 2162.7844, found 2162.7808.¹H-NMR (500 MHz, CDCl₃) 8.02-7.99 (m, 2H), 7.97-7.91 (m, 8H), 7.58-7.50(m, 6 H), 7.47-7.40 (m, 12H), 7.39-7.31 (m, 18H), 7.30-7.17 (m, 28H),7.17-7.09 (m, 16H), 7.03-7.0 (m, 5H), 7.0 (d, J=9.0 Hz, 2H), 6.79 (d,J=9.0 Hz, 2H), 5.96-5.81 (m, 2H), 5.66 (d, J=2.3 Hz, 1H), 5.44-5.40 (m,2H), 5.40-5.35 (m, 2H), 5.29 (d, J=8.8 Hz, 1H), 5.24-5.20 (m, 1H),5.20-5.13 (m, 2H), 5.0-4.89 (m, 3H), 4.88 (d, J=3.7 Hz, 1H), 4.85 (d,J=11.2 Hz, 1H), 4.81-4.75 (m, 10H), 4.75-4.72 (m, 8H), 4.72-4.66 (m,10H), 4.66-4.64 (m, 6H), 4.64-4.56 (m, 10H), 4.42-4.34 (m, 8H),4.32-4.23 (m, 6H), 4.23-4.14 (m, 5H), 4.11-4.05 (m, 6H), 4.03-3.97 (m,4H), 3.96-3.90 (m, 8H), 3.74 (s, 3H), 3.70-3.62 (m, 4H), 3.59 (s, 3H),3.54 (s, 3H), 3.50-3.44 (m, 2H), 3.44-3.38 (m, 2H), 3.36 (s, 3H), 3.35(s, 6H), 3.33 (s, 3H), 1.45 (s, 3H), 1.43 (s, 6H), 1.42 (s, 3H), 1.32(s, 6H); ¹³C-NMR (125 MHz, CDCl₃) δ 170.5, 170.4, 170.0, 169.3, 169.1,169.0, 165.5, 165.4, 155.4, 150.4, 138.5, 138.2, 138.1, 137.4, 137.1,136.9, 136.8, 133.9, 129.7, 129.6, 129.1, 129.0, 128.6, 128.4, 128.2,128.1, 127.9, 127.8, 127.7, 127.5, 127.4, 127.2, 118.1, 114.7, 98.5,98.2, 98.1, 97.7, 96.9, 96.8, 96.7, 80.0, 77.2, 77.0, 76.9, 76.7, 76.4,76.2, 75.1, 74.9, 74.8, 74.7, 74.5, 74.4, 74.1, 73.9, 73.8, 73.3, 73.2,73.0, 72.8, 72.7, 72.6, 72.5, 72.4, 72.1, 72.0, 71.2, 71.0, 70.8, 70.2,69.9, 69.7, 68.8, 68.6, 68.3, 67.4, 67.1, 66.7, 66.5, 66.4, 66.3, 66.2,61.4, 60.5, 55.6, 52.6, 52.4, 52.2, 51.8, 22.9, 22.7, 22.6, 20.9.

Synthesis of 69

Compound 69 is prepared from compound 63 following general procedure I:120 mg, 91%, R_(f)=0.3 (dichloromethane/methanol 19:1). ¹³C-NMR (125MHz, CDCl₃) δ 170.2, 170.1, 170.0, 167.9, 165.1, 165.0, 164.9, 155.7,150.9, 139.0, 138.3, 137.9, 137.2, 136.5, 133.9, 133.8, 133.6, 129.7,129.6, 129.3, 129.1, 128.9, 128.6, 128.5, 128.3, 128.25, 128.2, 128.1,128.0, 127.9, 127.8, 127.4, 118.6, 114.5, 100.9, 100.6, 100.5, 100.4,99.0, 98.6, 98.3, 98.2, 81.4, 81.3, 81.2, 81.1, 80.1, 77.8, 76.7, 76.4,76.3, 75.5, 75.2, 75.1, 75.0, 74.8, 74.7, 74.4, 74.2, 74.1, 74.0, 73.8,73.3, 72.6, 72.4, 72.35, 61.6, 60.1, 60.0, 55.6, 52.8, 52.65, 52.6,52.3, 52.1, 22.7, 22.65

General Procedure J (GPJ): O-Sulfation.

Sulfur trioxide trimethylamine complex (5 equiv per hydroxyl group) isadded to the starting materials in dry DMF (3 mL for 50 mg). The mixtureis heated at 50-60° C. under argon for 48-72 h. MeOH (1 mL) is added andthe mixture stirred for 15 min and concentrated in vacuo. Chromatography(dichloromethane:methanol:aq. ammonia, 7:2:0.5) affords O-sulfatedproducts.

General Procedure K (GPK): Saponification.

Starting material is dissolved in methanol and water (4/1, v/v, 1.25 mLfor 20 mg) containing 2M solution of sodium hydroxide (50 microL per1.25 mL of reaction mixture) at 0° C. The reaction mixture is stirred atroom temperature for 48-72 hours. After TLC (EtOAc:EtOH:water, 3:1:1)indicates the completion of the reaction, the volume of the solvents isreduced in vacuo. The solution is applied to a column of silica forflash chromatography (dichloromethane:methanol:aq. ammonia, 7:2:0.5) tofurnish the de-O-benzoylated products.

General Procedure L (GPL): Global Debenzylation.

Starting material is dissolved in THF and water (1/1, v/v, 3 mL for 10mg) containing aqueous ammonia solution (150 μL per 3 mL of reactionmixture) and treated with palladium hydroxide on carbon (20% Pd, 5 timesthe weight of starting material). The reaction mixture is stirred for24-48 hours under hydrogen at ambient temperature and pressure. AfterTLC (EtOAc:EtOH:water, 2:1:1) indicates the completion of the reactionthe catalyst is filtered off and washed with 50% aqueous THF. Thesolution is concentrated to dryness and chromatography of the residue(dichloromethane:methanol:aq. ammonia, 5:4:1) gives the final productsas ammonium salts. Some of the resulting materials are dissolved inwater, passed through a Dowex 50WX8-200 (Na⁺) resin column (8×1 cm) andeluted with water. Fractions containing the products are evaporated anddried in vacuo to furnish sodium salts of final products.

Synthesis of 70

Compound 70 is prepared from compound 64 following general procedure J:135 mg, 81% yield, Rf=0.2 (dichloromethane:methanol:aq. ammonia,7:2:0.5). HRMS (ESI) calcd for C₁₂₂H₁₃₁N₃O₄₇S₃Na (M+Na)⁺ m/z 2508.7013,found 2508.65. ¹H-NMR (500 MHz, MeOD) 8.13-8.08 (m, 4H), 8.02 (d, J=7.3Hz, 2H), 7.63 (q, J=7.0 Hz, 2H), 7.56 (t, J=7.6 Hz, 2H), 7.52 (q, J=9.8Hz, 2H), 7.44 (t, J=8.0 Hz, 2H), 7.34-7.28 (m, 8 H), 7.27-7.23 (m, 8H),7.22-7.17 (m, 8H), 7.16-7.13 (m, 6H), 7.12-7.07 (m, 6 H), 6.99 (d, J=9.1Hz, 2H), 6.84 (d, J=9.1 Hz, 2H), 5.74 (d, J=3.1 Hz, 1H), 5.61 (d, J=3.9Hz, 1H), 5.55 (d, J=3.9 Hz, 1H), 5.31 (t, J=3.7 Hz, 2H), 5.26-5.23 (m,2H), 5.23-5.20 (m, 2H), 5.08 (d, J=3.3 Hz, 2H), 5.04 (d, J=3.4 Hz, 1H),4.99 (d, J=3.3 Hz, 1H), 4.97 (d, J=3.1 Hz, 1H), 4.89-4.81 (m, 2H),4.80-4.77 (m, 2H), 4.75 (d, J=3.5 Hz, 1H), 4.73-4.69 (m, 3H), 4.68 (d,J=11.6 Hz, 1H), 4.61 (d, J=11.1 Hz, 1H), 4.49 (t, J=7.5 Hz, 2H),4.41-4.39 (m, 1H), 4.38-4.35 (m, 1H), 4.34-4.32 (m, 2H), 4.32-4.29 (m,1H), 4.28-4.22 (m, 2H), 4.21-4.18 (m, 1H), 4.17-4.14 (m, 2H), 4.13 (d,J=3.9 Hz, 1H), 4.10-4.07 (m, 1H), 4.04 (t, J=9.5 Hz, 2H), 4.0 (t, J=9.5Hz, 2H), 3.86-3.80 (m, 2H), 3.72 (s, 3H), 3.66 (t, J=7.2 Hz, 2H), 3.60(d, J=9.2 Hz, 1H), 3.55-3.49 (m, 2H), 3.49-3.46 (m, 1H), 3.45 (s, 3H),3.31 (s, 3H), 3.30 (s, 3H), 1.65 (s, 3H), 1.48 (s, 3H), 1.44 (s, 3H);¹³C-NMR (125 MHz, MeOD) δ 173.6, 173.3, 171.3, 171.1, 170.8, 167.4,167.3, 157.0, 151.9, 140.0, 139.8, 138.99, 138.9, 138.8, 134.8, 134.7,134.6, 131.2, 130.9, 130.8, 130.1, 130.0, 129.9, 129.6, 129.5, 129.4,129.3, 129.2, 129.1, 129.0, 128.9, 128.8, 128.7, 128.5, 128.4, 128.1,119.4, 115.7, 99.6, 99.4, 99.3, 98.4, 98.1, 97.3, 81.4, 79.8, 79.7,79.2, 76.1, 75.8, 75.6, 75.3, 75.2, 74.9, 74.6, 74.2, 74.1, 74.0, 73.3,72.9, 72.7, 72.2, 72.1, 71.9, 71.8, 71.7, 70.9, 70.6, 70.5, 67.3, 66.3,56.1, 54.3, 53.8, 53.2, 53.0, 52.9, 22.9, 22.8, 227.

Synthesis of 71

Compound 71 is prepared from compound 65 following general procedure J:86 mg, 99%, R_(f)=0.18 (dichloromethane/methanol/triethylamine 90:9:1).¹³C-NMR (125 MHz, CDCl₃) δ 170.6, 170.5, 170.2, 168.5, 168.3, 167.9,165.3, 165.2, 165.0, 155.7, 150.8, 139.1, 139.0, 138.6, 138.4, 137.1,136.7, 133.6, 133.5, 130.0, 129.7, 129.2, 129.1, 129.0, 128.8, 128.6,128.5, 128.4, 128.2, 128.1, 128.0, 127.8, 127.7, 127,6, 127.5, 127.4,127.3, 118.7, 114.5, 100.7, 100.0, 99.8, 98.1, 97.8, 96.8, 81.8, 81.6,81.4, 79.8, 77.8, 76.7, 76.6, 75.8, 75.2, 75.1, 74.85, 74.8, 74.7, 74.5,74.3, 74.2, 74.0, 73.9, 73.7, 73.6, 70.8, 70.5, 70.0, 65.6, 64.2, 64.0,55.6, 52.7, 52.4, 52.1, 52.0, 51.9, 46.5, 23.0, 22.8, 22.7, 8.9

Synthesis of 72

Compound 72 is prepared from compound 66 following general procedure J:13 mg, 78% yield, Rf=0.2 (dichloromethane:methanol:aq. ammonia,7:2:0.5). HRMS (ESI) calcd for C₁₅₈H₁₇₀N₄O₆₂S₄Na (M+Na)⁺ m/z 3265.9053,found 3265.8494. ¹H-NMR (500 MHz, MeOD) 8.13-8.08 (m, 6H), 8.01 (d,J=7.5 Hz, 2H), 7.63-7.59 (m, 2H), 7.59-7.54 (m, 2H), 7.53-7.47 (m, 2H),7.46-7.41 (m, 6H), 7.33-7.28 (m, 10 H), 7.28-7.22 (m, 15H), 7.22-7.18(m, 10H), 7.17-7.14 (m, 6H), 7.13 (d, J=7.4 Hz, 2H), 7.09 (d, J=7.2 Hz,2H), 6.99 (d, J=9.1 Hz, 2H), 6.84 (d, J=8.9 Hz, 2H), 5.73 (d, J=3.4 Hz,1H), 5.59 (d, J=3.9 Hz, 1H), 5.56-5.52 (m, 2H), 5.31-5.28 (m, 2H),5.25-5.17 (m, 3H), 5.07 (d, J=3.6 Hz, 1H), 5.03 (t, J=3.9 Hz, 2H), 4.99(d, J=3.9 Hz, 1H), 4.97-4.96 (m, 2H), 4.88 (d, J=3.0 Hz, 1H), 4.81-4.76(m, 3H), 4.74-4.72 (m, 2H), 4.72-4.70 (m, 2H), 4.70-4.68 (m, 3H),4.68-4.65 (m, 2H), 4.63 (d, J=11.5 Hz, 1H), 4.50 (d, J=10.4 Hz, 2H),4.39-4.32 (m, 6H), 4.32-4.28 (m, 4H), 4.27-4.22 (m, 4H), 4.21-4.17 (m,2H), 4.17-4.11 (m, 3H), 4.10 (t, J=3.8 Hz, 2H), 4.08 (t, J=3.8 Hz, 2H),4.03-3.98 (m, 3H), 3.98-3.94 (m, 2H), 3.84-3.79 (m, 2H), 3.73 (s, 3H),3.63-3.57 (m, 2H), 3.56-3.50 (m, 2H), 3.49-3.47 (m, 2H), 3.47 (s, 3H),3.30 (s, 3H), 3.28 (s, 3H), 3.27 (s, 3H), 1.65 (s, 3H), 1.49 (s, 3H),1.47 (s, 3H), 1.44 (s, 3H); ¹³C-NMR (125 MHz, MeOD) δ 173.6, 173.3,171.2, 170.8, 167.3, 157.0, 152.0, 140.0, 139.8, 138.9, 138.88, 138.83,138.7, 134.8, 134.6, 131.2, 130.8, 130.1, 130.0, 129.9, 129.5, 129.3,129.2, 129.1, 128.9, 128.8, 128.7, 128.5, 128.4, 128.2, 128.0, 119.5,115.8, 99.66, 99.4, 99.3, 99.1, 98.3, 98.0, 97.2, 81.4, 79.8, 79.1,76.1, 75.8, 75.6, 75.5, 74.2, 74.9, 74.6, 74.5, 74.2, 74.1, 73.3, 72.9,72.6, 72.5, 72.1, 71.8, 70.8, 70.7, 70.5, 67.2, 66.3, 56.1, 54.3, 53.8,53.2, 53.0, 22.9, 22.8, 22.7.

Synthesis of 73

Compound 73 is prepared from compound 67 following general procedure J:46 mg, quant., R_(f)=0.15 (dichloromethane/methanol/triethylamine90:9:1). ¹³C-NMR (125 MHz, CDCl₃) δ 170.5, 170.4, 170.1, 168.4, 168.35,168.3, 167.9, 165.3, 165.2, 165.0, 155.7, 150.8, 139.1, 139.0, 138.6,138.4, 137.1, 136.8, 133.6, 133.5, 130.1, 129.7, 129.2, 129.1, 129.0,128.8, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 127.8, 127.7, 127.6,127.5, 127.4, 118.7, 114.5, 100.7, 100.1, 99.9, 98.3, 97.8, 96.8, 81.7,81.4, 79.7, 77.8, 76.7, 76.6, 76.0, 75.2, 75.1, 74.9, 74.8, 74.7, 74.6,74.4, 74.3, 74.1, 73.9, 73.8, 73.7, 73.6, 70.9, 70.6, 70.1, 65.5, 64.1,64.0, 63.9, 55.6, 52.7, 52.6, 52.4, 52.2, 52.1, 52.0, 51.95, 51.9, 46.3,23.1, 22.8, 22.7, 9.8

Synthesis of 74

Compound 74 is prepared from compound 68 following general procedure J:25 mg, 94% yield, Rf=0.15 (dichloromethane:methanol:aq. ammonia,7:2:0.5). HRMS (ESI) calcd for C₁₉₄H₂₀₉N₅O₇₇S₅Na₃ (M+3Na)³⁺ m/z 4069.09,found 4070.2. ¹H-NMR (500 MHz, MeOD) 8.13-8.08 (m, 8H), 8.01 (d, J=8.9Hz, 2H), 7.64-7.59 (m, 6H), 7.59-7.54 (m, 6H), 7.53-7.45 (m, 4H),7.44-7.39 (m, 6H), 7.32-7.28 (m, 12 H), 7.28-7.21 (m, 14H), 7.21-7.19(m, 10H), 7.18-7.13 (m, 8H), 7.12-7.06 (m, 4H), 6.99 (d, J=9.5 Hz, 2H),6.84 (d, J=9.5 Hz, 2H), 5.73 (d, J=3.4 Hz, 1H), 5.59 (d, J=4.0 Hz, 1H),5.56-5.52 (m, 2H), 5.31-5.28 (m, 2H), 5.24-5.20 (m, 3H), 5.19-5.16 (m,3H), 5.08 (d, J=4.2 Hz, 1H), 5.03-5.0 (m, 2H), 4.99-4.96 (m, 2H), 4.87(d, J=2.9 Hz, 1H), 4.81-4.76 (m, 3H), 4.75-4.70 (m, 4H), 4.70-4.64 (m,5H), 4.62 (d, J=11.2 Hz, 1H), 4.49 (d, J=11.2 Hz, 2H), 4.39-4.34 (m,6H), 4.33-4.27 (m, 8H), 4.26-4.21 (m, 6H), 4.20-4.17 (m, 8H), 4.17-4.12(m, 8H), 4.11-4.04 (m, 2H), 4.03-3.96 (m, 3H), 3.84-3.80 (m, 2H), 3.74(s, 3H), 3.64-3.61 (m, 2H), 3.61-3.56 (m, 2H), 3.55-3.50 (m, 1H),3.48-3.43 (m, 2H), 3.47 (s, 3H), 3.31 (s, 3H), 3.30 (s, 3H), 3.28 (s,3H), 3.26 (s, 3H), 1.65 (s, 3H), 1.49 (s, 3H), 1.48 (s, 3H), 1.47 (s,3H), 1.43 (s, 3H); ¹³C-NMR (MeOD) δ 173.5, 170.8, 167.3, 158.1, 153.2,139.9, 138.8, 134.7, 131.2, 130.9, 129.9, 129.5, 129.3, 129.1, 128.9,128.8, 128.5, 128.4, 128.2, 128.0, 119.5, 115.8, 99.7, 99.5, 99.3, 99.2,98.5, 98.3, 97.2, 97.1, 79.9, 76.1, 75.5, 75.1, 74.5, 74.1, 71.9, 66.3,56.1, 53.8, 52.9, 49.6, 22.8.

Synthesis of 143

Compound 143 is prepared from compound 142 following general procedureJ: 132 mg, 27.7 μmol, 83% yield, R_(f)=0.15(dichloromethane:methanol:aq. ammonia, 7:2:0.5); HRMS (ESI) calcd forC₂₃₀H₂₄₈N₆O₉₂S₆Na₃ (M+3Na)⁺³ m/z 1608.0852, found 1608.0801. ¹H-NMR (500MHz, MeOD) 8.15-8.08 (m, 8H), 8.01 (d, J=8.6 Hz, 2H), 7.65-7.57 (m, 5H),7.55-7.44 (m, 8H), 7.44-7.40 (m, 6H), 7.35-7.28 (m, 24 H), 7.27-7.21 (m,18H), 7.20-7.14 (m, 16H), 7.14-7.05 (m, 8H), 6.99 (d, J=9.0 Hz, 2H),6.84 (d, J=9.0 Hz, 2H), 5.74 (d, J=4.3 Hz, 1H), 5.61 (d, J=3.0 Hz, 1H),5.58-5.53 (m, 3H), 5.32 (t, J=3.8 Hz, 2H), 5.26-5.21 (m, 2H), 5.21-5.16(m, 2H), 5.06 (d, J=3.4 Hz, 1H), 5.03-4.99 (m, 2H), 4.99 (d, J=3.4 Hz,1H), 4.96 (d, J=2.4 Hz, 1H), 4.88 (d, J=2.4 Hz, 1H), 4.82-4.73 (m, 3H),4.75-4.71 (m, 4H), 4.70-4.65 (m, 5H), 4.62 (d, J=11.0 Hz, 1H), 4.52-4.44(m, 8H), 4.39-4.35 (m, 10H), 4.35-4.27 (m, 12H), 4.26-4.18 (m, 6H),4.18-4.11 (m, 12H), 4.11-4.04 (m, 4H), 4.04-3.95 (m, 4H), 3.87-3.81 (m,2H), 3.73 (s, 3H), 3.71 (s, 3H), 3.69 (s, 6H), 3.64-3.57 (m, 4H),3.56-3.51 (m, 2H), 3.31 (s, 3H), 3.30 (s, 6H), 3.29 (d, J=4.5 Hz, 1H),1.67 (s, 3H), 1.51 (s, 3H), 1.50 (s, 6H), 1.49 (s, 3H), 1.46 (s, 3H);¹³C-NMR (125 MHz, MeOD) δ 173.5, 173.3, 171.2, 170.9, 167.5, 167.4,167.3, 164.9, 157.1, 152.0, 140.0, 139.9, 139.0, 138.9, 138.8, 138.7,134.9, 134.7, 131.2, 130.9, 130.8, 130.0, 129.6, 129.3, 129.2, 129.17,129.12, 129.0, 128.9, 128.7, 128.6, 128.4, 128.2, 119.5, 115.8, 99.7,99.3, 98.5, 98.4, 98.2, 97.4, 81.4, 79.8, 79.2, 76.2, 76.1, 76.0, 75.6,75.2, 74.6, 74.2, 74.0, 73.5, 73.1, 72.7, 72.6, 72.2, 72.1, 71.9, 70.9,70.7, 70.6, 67.3, 66.3, 56.2, 55.2, 54.3, 53.8, 53.2, 53.1, 52.9, 48.6,22.9, 22.8, 22.7.

Synthesis of 145

Compound 145 is prepared from compound 80 following general procedure J:69 mg, 18.1 μmol, 98% yield, R_(f)=0.15 (dichloromethane:methanol:aq.ammonia, 7:2:0.5); HRMS (ESI) calcd for C₁₅₄H₁₇₈N₅O₈₇S₁₀NH₄ (M−4H)⁻⁴ m/z956.1735, found 956.1740. ¹H-NMR (500 MHz, MeOD) 7.45-7.42 (m, 4H),7.35-7.31 (m, 6H), 7.30-7.27 (m, 18H), 7.26-7.22 (m, 12 H), 7.22-7.19(m, 10H), 7.19-7.15 (m, 5H), 7.07 (d, J=9.0 Hz, 2H), 6.85 (d, J=9.1 Hz,2H), 5.88 (d, J=3.0 Hz, 1H), 5.60-5.56 (m, 2H), 5.02-4.93 (m, 5H),4.92-4.74 (m, 12H), 4.74-4.70 (m, 3H), 4.70-4.61 (m, 6H), 4.59-4.49 (m,5H), 4.39-4.33 (m, 8H), 4.33-4.23 (m, 10H), 4.23 (d, J=9.5 Hz, 1H),4.19-4.16 (m, 6H), 4.16-4.13 (m, 6H), 4.13 (d, J=3.5 Hz, 1H), 4.08-4.03(m, 4H), 4.02-3.99 (m, 2H), 3.98-3.96 (m, 1H), 3.96-3.92 (m, 2H),3.90-3.82 (m, 3H), 3.81-3.78 (m, 2H), 3.73 (s, 3H), 3.66-3.61 (m, 2H),3.31 (s, 3H), 3.309 (s, 3H), 3.306 (s, 3H), 3.303 (s, 3H), 3.29 (s, 3H),1.96 (s, 3H), 1.93 (s, 6H), 1.92 (s, 3H); ¹³C-NMR (125 MHz, MeOD) δ175.9, 174.1, 159.2, 156.6, 152.1, 140.3, 139.7, 139.2, 138.7, 129.7,129.6, 129.5, 129.4, 129.3, 129.1, 128.9, 128.8, 128.7, 128.6, 128.2,119.4, 115.7, 99.7, 99.6, 99.5, 99.4, 99.2, 98.9, 81.8, 79.3, 76.3,75.3, 74.0, 72.8, 72.7, 72.6, 71.5, 69.3, 67.9, 67.2, 56.1, 54.5, 49.5,41.0, 23.3.

Synthesis of 146

Compound 146 is prepared from compound 144 following general procedureJ: 69 mg, 18.1 μmol, 98% yield, R_(f)=0.15 (dichloromethane:methanol:aq.ammonia, 7:2:0.5); HRMS (ESI) calcd for C₁₈₂H₂₁₂N₆O₁₀₄S₁₂Na (M+Na)⁺ m/z4553.81, found 4553.01. ¹H-NMR (500 MHz, MeOD) 7.46-7.41 (m, 4H),7.35-7.31 (m, 6H), 7.30-7.27 (m, 24H), 7.26-7.23 (m, 16 H), 7.22-7.18(m, 10H), 7.18-7.13 (m, 5H), 7.07 (d, J=8.9 Hz, 2H), 6.84 (d, J=9.0 Hz,2H), 5.88 (d, J=3.0 Hz, 1H), 5.61-5.55 (m, 2H), 5.04-4.94 (m, 5H),4.93-4.74 (m, 12H), 4.74-4.69 (m, 3H), 4.69-4.60 (m, 6H), 4.59-4.46 (m,5H), 4.41-4.35 (m, 10H), 4.33-4.26 (m, 10H), 4.26 (d, J=11.0 Hz, 1H),4.2-4.11 (m, 8H), 4.08-4.03 (m, 5H), 4.03 (d, J=9.8 Hz, 1H), 3.98-3.96(m, 5H), 3.96-3.92 (m, 5H), 3.91-3.85 (m, 3H), 3.83-3.80 (m, 2H),3.80-3.77 (m, 2H), 3.76-3.73 (m, 1H), 3.73 (s, 3H), 3.66-3.61 (m, 2H),3.313 (s, 3H), 3.31 (s, 3H), 3.306 (s, 6H), 3.303 (s, 3H), 3.3 (s, 3H),1.97 (s, 6H), 1.95 (s, 3H), 1.94 (s, 6H), 1.92 (s, 3H); ¹³C-NMR (125MHz, MeOD) δ 176.0, 175.5, 174.1, 159.2, 156.6, 152.1, 140.3, 139.7,139.1, 138.7, 129.7, 129.5, 129.3, 129.2, 129.0, 128.9, 128.8, 128.7,128.6, 128.5, 128.2, 119.4, 115.7, 99.7, 99.6, 99.5, 99.4, 98.9, 98.2,96.7, 81.8, 79.3, 76.3, 75.3, 74.0, 72.7, 72.6, 72.5, 72.2, 71.5, 70.0,69.3, 68.0, 67.2, 56.1, 54.5, 49.5, 41.0, 23.3.

Synthesis of 75

Compound 75 is prepared from compound 69 following general procedure J:130 mg, quant., R_(f)=0.15 (dichloromethane/methanol/triethylamine90:9:1); MS (ESI, negative mode) calcd for C₁₉₄H₂₀₉N₅O₇₇S₅(M−5HNEt₃+2H)²⁻ m/z (%): 1999.05 (30), 1999.55 (70), 2000.05 (100),2000.55 (90), 2001.06 (65), 2001.56 (25) found 1999.05 (30), 1999.55(70), 2000.05 (90), 2000.55 (80), 2001.05 (65), 2001.55 (35). ¹³C-NMR(125 MHz, CDCl₃) δ 170.35, 170.3, 168.5, 168.3, 168.25, 168.2, 167.9,165.2, 165.1, 155.6, 150.9, 139.1, 138.6, 138.4, 137.0, 133.4, 130.0,129.7, 129.3, 129.1, 129.0, 128.8, 128.5, 128.4, 128.3, 128.2, 128.0,127.9, 127.8, 127.7, 127.6, 127.5, 127.3, 127.2, 118.6, 114.4, 100.4,100.0, 99.9, 98.3, 97.5, 96.8, 81.9, 81.4, 79.8, 77.7, 76.4, 76.0, 75.0,74.9, 74.8, 74.6, 74.5, 74.4, 74.1, 74.0, 73.7, 73.5, 70.9, 70.4, 70.0,65.4, 63.9, 55.6, 54.5, 52.6, 52.1, 51.85, 51.8, 46.3, 23.1, 22.8, 8.6

Synthesis of 76

Compound 76 is prepared from compound 70 following general procedure K:52 mg, 81% yield, Rf=0.2 (EtOAc:EtOH:water, 3:1:1). HRMS (ESI) calcd forC₉₈H₁₁₃N₃O₄₄S₃Na₂ (M+2Na)²⁺ m/z 2177.5654, found 2177.62. ¹H-NMR (500MHz, MeOD) 7.44-7.40 (m, 3H), 7.39-7.35 (m, 5 H), 7.34-7.31 (m, 5H),7.29-7.26 (m, 5H), 7.26-7.21 (m, 8H), 7.20-7.17 (m, 6H), 7.15-7.13 (m, 3H), 7.09 (d, J=8.9 Hz, 2H), 6.85 (d, J=8.9 Hz, 2H), 5.49 (d, J=4.0 Hz,1H), 5.30 (d, J=4.6 Hz, 1H), 5.25 (d, J=4.3 Hz, 1H), 4.87-4.77 (m, 6H),4.76-4.74 (m, 2H), 4.73-4.68 (m, 2H), 4.67-4.65 (m, 2H), 4.65-4.61 (m,3H), 4.61 (d, J=4.6 Hz, 1H), 4.46 (d, J=10.7 Hz, 1H), 4.40 (d, J=11.5Hz, 1H), 4.34-4.29 (m, 6H), 4.26-4.17 (m, 8H), 4.13-4.04 (m, 5H),4.0-3.95 (m, 3H), 3.94-3.84 (m, 2H), 3.82-3.77 (m, 2H), 3.73 (s, 3H),3.71-3.65 (m, 2H), 3.65-3.59 (m, 2H), 1.79 (s, 3H), 1.69 (s, 3H), 1.66(s, 3H); ¹³C-NMR (125 MHz, MeOD) δ 173.2, 156.5, 152.4, 139.9, 139.8,139.5, 139.1, 129.6, 129.5, 129.3, 129.0, 128.8, 128.75, 128.7, 128.6,119.2, 115.7, 101.7, 100.9, 100.5, 99.2, 98.1, 82.2, 79.1, 76.2, 76.1,74.9, 73.0, 71.6, 68.6, 67.6, 67.3, 56.1, 54.3, 49.5, 22.9.

Synthesis of 77

Compound 77 is prepared from compound 71 following general procedure K:29 mg, 72%, R_(f)=0.15 (EtOAc/ethanol/water 3:1:1). ¹³C-NMR (125 MHz,methanol-D4, HSQC) δ 129.6, 129.3, 129.2, 129.1, 128.5, 119.4, 115.5,104.1, 103.8, 98.1, 86.3,82.1, 80.9, 79.4, 78.6, 77.9, 76.4, 76.3, 75.9,75.8, 75.6, 75.3, 75.2, 75.1, 74.9, 74.8, 71.2, 67.4, 67.0, 56.1, 54.6,53.9, 47.4, 23.0, 9.7

Synthesis of 78

Compound 78 is prepared from compound 72 following general procedure K:29 mg, 85% yield, R_(f)=0.22 (EtOAc:EtOH:water, 3:1:1). HRMS (ESI) calcdfor C₁₂₆H₁₄₆N₄O₅₈S₄Na (M+Na)⁺ m/z 2793.7379, found 2793.7398. ¹H-NMR(500 MHz, MeOD) 7.43-7.40 (m, 4H), 7.40-7.36 (m, 5 H), 7.35-7.31 (m,8H), 7.30-7.25 (m, 10H), 7.25-7.22 (m, 8H), 7.21-7.15 (m, 6H), 7.15-7.11(m, 4 H), 7.09 (d, J=9.0 Hz, 2H), 6.85 (d, J=9.0 Hz, 2H), 5.48 (d, J=3.4Hz, 1H), 5.27 (d, J=3.9 Hz, 1H), 5.24 (d, J=4.5 Hz, 1H), 5.21 (d, J=4.5Hz, 1H), 4.87-4.85 (m, 3H), 4.84-4.77 (m, 4H), 4.77-4.74 (m, 2H),4.74-4.70 (m, 2H), 4.70-4.68 (m, 2H), 4.66-4.60 (m, 3H), 4.45-4.43 (m,1H), 4.43-4.41 (m, 1H), 4.40-4.38 (m, 1H), 4.38-4.34 (m, 5H), 4.34-4.32(m, 3H), 4.32-4.30 (m, 4H), 4.29-4.27 (m, 2H), 4.27-4.25 (m, 3H),4.25-4.20 (m, 4H), 4.19 (d, J=3.7 Hz, 1H), 4.17 (d, J=3.1 Hz, 1H),4.13-4.05 (m, 4H), 4.04 (t, J=4.1 Hz, 2H), 4.01 (d, J=4.1 Hz, 1H),3.97-3.93 (m, 3H), 3.92-3.83 (m, 4H), 3.82-3.76 (m, 2H), 3.74 (s, 3H),3.73-3.68 (m, 2H), 3.67-3.60 (m, 2H), 1.80 (s, 3H), 1.66 (s, 3H), 1.63(s, 3H), 1.62 (s, 3H); ¹³C-NMR (125 MHz, MeOD) δ 176.5, 175.7, 175.4,156.7, 155.8, 154.1, 139.8, 139.1, 129.7, 129.6, 129.5, 129.4, 129.3,129.2, 129.1, 128.9, 128.8, 128.7, 128.5, 119.3, 115.7, 102.4, 102.3,101.8, 101.7, 101.6, 100.1, 97.9, 97.8, 87.3, 86.5, 81.7, 81.1, 76.6,76.2, 76.1, 73.1, 72.9, 71.6, 69.5, 68.7, 67.4, 56.1, 54.4, 53.9, 53.5,22.9.

Synthesis of 79

Compound 79 is prepared from compound 73 following general procedure K:29 mg, 94%, R_(f)=0.6 (EtOAc/ethanol/water 2:2:1). ¹³C-NMR (125 MHz,methanol-D4) δ 176.6, 175.8, 175.3, 173.1, 173.0, 155.9, 153.2, 140.3,139.9, 139.6, 129.9, 129.5, 129.4, 129.2, 129.1, 128.6, 128.5, 119.6,115.5, 104.1, 104.0, 103.9, 98.6, 98.2, 98.0, 86.4, 86.1, 85.8, 81.8,80.5, 79.3, 78.3, 78.2, 77.6, 76.6, 76.2, 75.9, 75.8, 75.7, 75.3, 75.1,74.9, 74.8, 74.6, 71.3, 71.2, 71.1, 67.4, 67.1, 56.1, 54.4, 53.5, 53.4,53.3, 23.0

Synthesis of 80

Compound 80 is prepared from compound 74 following general procedure K:14 mg, 82% yield, R_(f)=0.21 (EtOAc:EtOH:water, 3:1:1). ¹H-NMR (500 MHz,MeOD) 7.43-7.40 (m, 5H), 7.39-7.35 (m, 6 H), 7.35-7.30 (m, 12H),7.29-7.23 (m, 16H), 7.22-7.15 (m, 12H), 7.15-7.13 (m, 4 H), 7.09 (d,J=9.0 Hz, 2H), 6.85 (d, J=9.2 Hz, 2H), 5.47 (d, J=4.0 Hz, 1H), 5.27 (d,J=3.9 Hz, 1H), 5.24-19 (m, 3H), 4.94-4.75 (m, 8H), 4.74-4.72 (m, 6H),4.72-4.69 (m, 2H), 4.69-4.67 (m, 4H), 4.66-4.60 (m, 3H), 4.46-4.42 (m,8H), 4.41-4.38 (m, 10H), 4.37-4.34 (m, 4H), 4.33-4.28 (m, 5H), 4.27-4.23(m, 6H), 4.23-4.17 (m, 8H), 4.14-4.06 (m, 4H), 4.04-3.97 (m, 3H),3.93-3.82 (m, 4H), 3.80-3.76 (m, 3H), 3.74 (s, 3H), 3.73-3.66 (m, 2H),3.66-3.63 (m, 2H), 1.81 (s, 3H), 1.65 (s, 3H), 1.62 (s, 6H), 1.61 (s,3H); ¹³C-NMR (125 MHz, MeOD) δ 8 173.2, 156.5, 152.5, 139.9, 139.5,139.2, 129.7, 129.6, 129.4, 129.1, 129.0, 128.9, 128.9, 128.8, 128.7,128.5, 119.2, 115.7, 101.7, 100.8, 99.9, 99.8, 79.2, 76.1, 72.9, 71.6,70.5, 69.2, 56.1, 55.1, 54.4, 49.6, 30.9, 30.7, 22.9.

Synthesis of 144

Compound 144 is prepared from compound 143 following general procedureK: 85 mg, 20.98 μmol, 76% yield, R_(f)=0.2 (EtOAc:EtOH:water, 3:1:1);HRMS (ESI) calcd for C₁₈₂H₂₁₀N₆O₈₆S₆Na₂ (M+2Na)⁺² m/z 2046.5131, found2046.5109. ¹H-NMR (500 MHz, MeOD) 7.43-7.38 (m, 4H), 7.36-7.32 (m, 6 H),7.32-7.29 (m, 24H), 7.30-7.25 (m, 20H), 7.25-7.23 (m, 6H), 7.23-7.18 (m,5 H), 7.09 (d, J=8.9 Hz, 2H), 6.84 (d, J=8.9 Hz, 2H), 5.49-5.47 (m, 2H),5.40 (d, J=5.3 Hz, 1H), 5.34-5.32 (m, 2H), 5.28-5.25 (m, 4H), 5.24-5.21(m, 3H), 5.03-4.79 (m, 12H), 4.79-4.75 (m, 6H), 4.75-4.73 (m, 4H),4.73-4.67 (m, 6H), 4.66-4.59 (m, 7H), 4.66-4.60 (m, 3H), 4.49-4.41 (m,8H), 4.39-4.31 (m, 8H), 4.31-4.24 (m, 5H), 4.24-4.19 (m, 6H), 4.17-4.12(m, 3H), 4.11-4.05 (m, 5H), 4.05-3.98 (m, 3H), 3.94-3.81 (m, 4H),3.79-3.74 (m, 3H), 3.73 (s, 3H), 3.66-3.62 (m, 3H), 1.82 (s, 3H), 1.66(s, 3H), 1.628 (s, 6H), 1.621 (s, 3H), 1.61 (s, 3H); ¹³C-NMR (125 MHz,MeOD) δ 175.8, 173.3, 156.5, 152.4, 140.2, 140.1, 139.9, 139.7, 139.5,139.2, 139.1, 130.5, 129.9, 129.7, 129.6, 129.5, 129.3, 129.2, 129.1,128.9, 128.8, 128.7, 128.6, 101.7, 98.1, 101.8, 101.7, 99.7, 99.6, 98.4,98.3, 98.1, 82.2, 80.8, 79.2, 76.9, 76.5, 76.3, 75.9, 75.3, 74.9, 73.0,72.8, 72.3, 71.5, 70.7, 70.3, 69.8, 68.4, 67.6, 56.2, 55.2, 54.3, 49.9,39.3, 22.9.

Synthesis of 81

Compound 81 is prepared from compound 75 following general procedure K:75 mg, 75%, R_(f)=0.05 (EtOAc/ethanol/water 3:1:1). MS (ESI, negativemode) calcd for C₁₅₄H₁₆₉N₅O₇₂S₅ (M−10HNEt₃+8H)²⁻ m/z (%): 1703.95 found1703.93. ¹³C-NMR (125 MHz, methanol-D4) δ 175.9, 175.2, 174.4, 173.1,172.9, 156.9, 153.2, 140.4, 140.3, 139.9, 139.6, 129.5, 129.4, 139.35,129.3, 129.2, 129.0, 128.6, 128.5, 119.6, 115.5, 104.1, 104.05, 104.0,103.9, 98.7, 98.2, 86.4, 86.1, 85.8, 81.9, 80.4, 80.2, 79.3, 78.2, 77.9,77.7, 76.6, 76.5, 76.3, 75.9, 75.8, 75.7, 75.6, 75.3, 75.2, 75.1, 74.7,71.4, 71.1, 67.3, 67.0, 56.1, 54.3, 53.4, 22.9

Synthesis of 82

Compound 82 is prepared from compound 78 following general procedure J:24 mg, 90% yield, Rf=0.15 (dichloromethane:methanol:aq. ammonia,7:2:0.5). ¹H-NMR (500 MHz, MeOD) 7.47-7.42 (m, 4H), 7.40-7.35 (m, 6H),7.35-7.31 (m, 8 H), 7.30-7.25 (m, 6H), 7.25-7.20 (m, 7H), 7.20-7.15 (m,8H), 7.14-7.11 (m, 6H), 7.08 (d, J=8.3 Hz, 2H), 6.85 (d, J=9.0 Hz, 2H),5.89-5.86 (m, 1H), 5.62-5.57 (m, 1H), 5.55 (d, J=9.8 Hz, 1H), 5.49 (d,J=6.9 Hz, 1H), 5.44-5.40 (m, 4H), 5.39-5.36 (m, 3H), 5.35-5.32 (m, 4H),5.29-5.27 (m, 3H), 5.26 (t, J=9.8 Hz, 2H),), 4.99-4.75 (m, 3H),4.75-4.72 (m, 4H), 4.71-4.67 (m, 2H), 4.67-4.59 (5H), 4.59-4.50 (m, 8H),4.38-4.28 (m, 6H), 4.27-4.13 (m, 4H), 4.12-4.01 (m, 6H), 4.0-3.81 (m,2H), 3.80-3.76 (m, 2H), 3.74 (s, 3H), 3.72-3.67 (m, 2H), 3.67-3.60 (m,2H), 1.62 (s, 3H), 1.61 (s, 3H), 1.49 (s, 3H), 1.48 (s, 3H); ¹³C-NMR(125 MHz, MeOD) δ 174.1, 173.3, 156.6, 140.2, 139.8, 139.1, 139.0,138.6, 129.7, 129.5, 129.3, 129.28, 129.2, 129.1, 129.0, 128.9, 128.8,128.3, 128.2, 119.4, 115.7, 99.5, 99.2, 99.1, 99.0, 98.7, 98.5, 76.2,76.1, 73.7, 73.1, 71.6, 68.9, 67.4, 56.1, 54.4, 53.8, 23.3, 22.9.

Synthesis of 83

Compound 83 is prepared from compound 79 following general procedure J:15 mg, quant. ¹³C-NMR (125 MHz, methanol-D4, HSQC) δ 130.0, 129.9,129.5, 129.4, 129.2, 128.8, 120.1, 115.5, 102.4, 101.6, 101.5, 98.6,97.5, 97.4, 83.9, 81.9, 81.5, 81.1, 81.0, 80.4, 79.8, 79.6, 79.3, 78.2,76.6, 76.5, 76.1, 76.0, 75.9, 75.6, 75.5, 75.0, 74.9, 74.8, 74.5, 74.4,74.3, 73.9, 71.6, 71.4, 71.3, 67.4, 67.0, 66.8, 56.2, 53.4, 52.9, 22.1

Synthesis of 84

Compound 84 is prepared from compound 76 following general procedure L:9 mg, 85% yield, Rf=0.2 (EtOAc:EtOH:water, 2:1:1). HRMS (ESI) calcd forC₄₉H₇₁N₃O₄₄S₃Na (M+Na)⁺ m/z 1547.2368, found 1547.26. ¹H-NMR (500 MHz,D₂O) 7.13 (d, J=9.2 Hz, 2H), 6.98 (d, J=9.1 Hz, 2H), 5.45 (d, J=3.2 Hz,1H), 5.16 (d, J=3.8 Hz, 1H), 5.14 (d, J=3.8 Hz, 1H), 4.98 (d, J=3.2 Hz,1H), 4.89-4.86 (m, 1H), 4.75 (d, J=3.2 Hz, 1H), 4.33 (d, J=3.0 Hz, 1H),4.30 (d, J=3.0 Hz, 1H), 4.23 (d, J=13.0 Hz, 1H), 4.17-4.15 (m, 4H), 4.11(t, J=3.5 Hz, 2H), 4.08-4.04 (m, 5H), 4.04-4.02 (m, 2H), 4.01-3.92 (m,5H), 3.93 (d, J=3.5 Hz, 1H), 3.91-3.88 (m, 2H), 3.88-3.84 (m, 3H), 3.79(s, 3H), 3.75-3.70 (m, 4H), 3.69-3.67 (m, 2H), 3.67-3.65 (m, 2H),3.65-3.63 (m, 2H), 3.56-3.55 (m, 1H), 3.54-3.53 (m, 1H), 3.52-3.51 (m,1H), 1.99 (s, 6H), 1.98 (s, 3H); ¹³C-NMR (125 MHz, D₂O) δ 174.5, 174.4,1742, 154.8, 150.3, 119.3, 115.2, 101.9, 101.8, 100.7, 100.6, 94.9,77.1, 76.8, 74.2, 74.1, 73.9, 71.1, 70.4, 69.9, 69.4, 69.2, 69.18, 69.1,68.9, 68.8, 68.5, 68.4, 67.9, 66.5, 66.2, 55.9, 53.6, 53.4, 48.9, 22.0.

Synthesis of 85

Compound 85 is prepared from compound 77 following general procedure L:4 mg, 92%, R_(f)=0.1 (EtOAc/ethanol/water 2:2:1). ¹³C-NMR (125 MHz, D₂O)δ 175.0, 174.9, 174.7, 174.5, 174.3, 154.8, 151.0, 118.4, 115.1, 102.1,102.0, 101.3, 97.0, 96.7, 77.7, 77.3, 76.8, 76.5, 76.4, 76.3, 76.1,76.0, 73.6, 73.5, 73.4, 70.7, 70.1, 69.1, 69.0, 68.8, 68.5, 67.9, 66.4,65.8, 55.9, 53.6, 53.1, 22.0

Synthesis of 86

Compound 86 is prepared from compound 78 following general procedure L:4 mg, 94% yield, Rf=0.2 (EtOAc:EtOH:water, 2:1:1). HRMS (ESI) calcd forC₆₃H₉₂N₄O₅₈S₄Na₃ (M+3Na)³⁺ m/z 2029.2948, found 2029.2834. ¹H-NMR (500MHz, D₂O) 7.13 (d, J=9.2 Hz, 2H), 6.98 (d, J=9.2 Hz, 2H), 5.47 (d, J=3.4Hz, 1H), 5.17 (d, J=4.2 Hz, 1H), 5.14 (d, J=3.4 Hz, 1H), 4.99-4.96 (m,2H), 4.96 (d, J=3.41 Hz, 1H), 4.81 (d, J=2.3 Hz, 1H), 4.77 (d, J=3.0 Hz,1H), 4.73-4.65 (m, 3H), 4.33-4.30 (m, 3H), 4.30 (d, J=3.7 Hz, 1H),4.22-4.20 (m, 2H), 4.19-4.17 (m, 4H), 4.17-4.15 (m, 2H), 4.12 (t, J=3.0Hz, 2H), 4.08-4.04 (m, 5H), 4.04-4.02 (m, 4H), 4.0-3.94 (m, 5H),3.94-3.89 (m, 4H), 3.89-3.86 (m, 2H), 3.83-3.81 (m, 3H), 3.79 (s, 3H),3.75-3.69 (m, 4H), 3.68-3.67 (m, 2H), 3.66-3.65 (m, 2H), 3.64-3.63 (m,2H), 3.57-3.56 (m, 1H), 3.55-3.54 (m, 1H), 3.53-3.52 (m, 1H), 1.99 (s,6H), 1.98 (s, 6H); ¹³C-NMR (125 MHz, D₂O) δ 119.1, 115.3, 101.9, 100.0,98.8, 98.5, 76.7, 76.5, 76.3, 76.2, 76.1, 76.0, 7456, 73.3, 73.2, 69.2,69.0, 68.9, 68.8, 65.9, 55.9, 53.5, 22.0.

Synthesis of 87

Compound 87 is prepared from compound 79 following general procedure L:15 mg, 69%, R_(f)=0.1 (EtOAc/ethanol/water 2:2:1). ¹³C-NMR (125 MHz,D₂O, HSQC) δ 118.4, 115.1, 102.1, 101.1, 96.8, 77.5, 76.6, 76.3, 76.2,76.1, 76.0, 75.9, 73.6, 73.4, 73.2, 70.6, 69.1, 69.0, 68.8, 68.7, 66.4,65.8, 55.9, 53.1, 22.0

Synthesis of 88

Compound 88 is prepared from compound 80 following general procedure L:6 mg, 93% yield, Rf=0.15 (EtOAc:EtOH:water, 2:1:1). HRMS (ESI) calcd forC₇₇H₁₁₃N₅O₇₂S₅Na (M+Na)⁺ m/z 2442.38, found 2442.0. ¹H-NMR (500 MHz,D₂O) 7.16 (d, J=8.9 Hz, 2H), 7.01 (d, J=8.9 Hz, 2H), 5.47 (d, J=4.0 Hz,1H), 5.18 (d, J=4.2 Hz, 1H), 4.99 (d, J=3.5 Hz, 1H), 4.84 (d, J=3.8 Hz,1H), 4.73-4.69 (m, 3H), 4.36-4.30 (m, 5H), 4.24 (d, J=11.5 Hz, 1H),4.18-4.16 (m, 5H), 4.12-4.09 (m, 6H), 4.09-4.03 (m, 10H), 4.03-3.95 (m,12H), 3.94-3.92 (m, 8H), 3.92-3.86 (m, 6H), 3.81 (s, 3H), 3.78-3.68 (m,10H), 3.59-3.57 (m, 2H), 3.57-3.55 (m, 2H), 3.54-3.53 (m, 2H), 2.0 (s,15H); ¹³C-NMR (125 MHz, D₂O) δ 174.5, 174.4, 154.8, 119.3, 115.2, 101.9,101.8, 100.7, 100.6, 94.7, 76.8, 74.3, 73.9, 71.1, 70.3, 69.9, 69.8,69.4, 69.2, 69.1, 68.7, 68.6, 66.2, 55.9, 53.6, 22.0.

Synthesis of 147

Compound 147 is prepared from compound 144 following general procedureL: 26 mg, 9.03 μmol, 91% yield; R_(f)=0.15 (EtOAc:EtOH:water, 2:1:1);HRMS (ESI) calcd for C₉₁H₁₂₅N₆O₈₆S₆Na₉ (M−3H)³⁻ m/z 1024.7598, found:1024.7605. ¹H-NMR (500 MHz, D₂O) 7.16 (d, J=8.1 Hz, 2H), 7.0 (d, J=8.1Hz, 2H), 5.50 (d, J=3.4 Hz, 1H), 5.19 (bd, 1H), 5.16-5.12 (m, 3H),5.04-4.99 (m, 3H), 4.9-4.86 (m, 1H), 4.76-4.74 (m, 2H), 4.74-4.68 (m,5H), 4.68-4.65 (m, 2H), 4.35-4.28 (m, 5H), 4.26-4.18 (m, 6H), 4.16-4.13(m, 1H), 4.11-4.06 (m, 8H), 4.03-3.97 (m, 10H), 3.97-3.90 (m, 12H), 3.81(s, 3H), 3.78-3.70 (m, 12H), 3.68-3.64 (m, 2H), 3.64-3.63 (m, 2H),3.63-3.62 (m, 2H), 3.59-3.58 (m, 1H), 3.57-3.55 (m, 1H), 3.55-3.54 (m,1H), 3.53-3.50 (m, 1H), 2.01 (s, 18H); ¹³C-NMR (125 MHz, D₂O) δ 174.5,173.5, 119.2, 115.2, 101.9, 101.8, 100.6, 95.2, 95.1, 77.2, 74.2, 73.9,70.0, 69.9, 69.6, 69.4, 69.2, 69.1, 68.9, 68.1, 66.2, 55.9, 53.6, 22.1.

Synthesis of 89

Compound 89 is prepared from compound 81 following general procedure L:9 mg, 41%, R_(f)=0.1 (EtOAc/ethanol/water 2:2:1); MS (ESI, neg. mode)calcd for C₇₇H₁₁₃N₅O₇₂S₅Na (M−9Na+8H)⁻ m/z 2440.37, 2441.37, 2442.37,2443.37, 2444.37, found 2440.38, 2441.37, 2442.40, 2443.38, calcd forC₇₇H₁₁₃N₅O₇₂S₅Na (M−10Na+9H)⁻ m/z 2418.39, 2419.39, 2420.39, 2421.39,2422.39, found 2418.39, 2419.42, 2420.38, 2421.43, 2422.38. ¹³C-NMR (125MHz, D₂O) δ 175.4, 175.1, 174.6, 174.4, 154.9, 118.5, 115.2, 102.1,102.0, 96.8, 77.7, 77.5, 76.8, 76.6, 76.5, 76.4, 76.3, 76.2, 73.6, 70.7,70.1, 69.1, 68.8, 65.9, 61.3, 55.9, 53.6, 53.1, 22.0

Synthesis of 90

Compound 90 is prepared from compound 82 following general procedure L:11 mg, 78% yield, Rf=0.15 (EtOAc:EtOH:water, 2:1:1). HRMS (ESI) calcdfor C₆₃H₈₆N₄O₇₀S₈Na₁₀ (M+4H)⁴⁺ m/z 626.0008, found 626.001. ¹H-NMR (500MHz, D₂O) 7.15 (d, J=9.2 Hz, 2H), 6.99 (d, J=9.2 Hz, 2H), 5.68 (d, J=3.6Hz, 1H), 5.18-5.15 (m, 2H), 5.14 (d, J=3.6 Hz, 1H), 5.0-4.93 (m, 2H),4.89-4.86 (m, 2H), 4.84-4.80 (m, 4H), 4.78 (d, J=3.6 Hz, 1H), 4.73-4.63(m, 3H), 4.47 (d, J=4.1 Hz, 1H), 4.35-4.26 (m, 6H), 4.26-4.21 (m, 8H),4.19-4.17 (m, 4H), 4.16-4.15 (m, 2H), 4.12-4.10 (m, 2H), 4.07-4.0 (m,10H), 4.0-3.93 (m, 8H), 3.92-3.86 (m, 5H), 3.79 (s, 3H), 3.77-3.73 (m,4H), 3.73-3.68 (m, 2H), 3.68-3.66 (m, 2H), 3.66-3.65 (m, 2H), 3.64 (d,J=2.4 Hz, 1H), 3.62-3.61 (m, 1H), 3.56 (d, J=4.3 Hz, 1H), 3.54 (d, J=4.5Hz, 1H), 3.52 (d, J=4.6 Hz, 1H), 2.04 (s, 3H), 2.03 (s, 3H), 1.99 (s,3H), 1.98 (s, 3H); ¹³C-NMR (125 MHz, D₂O) δ 174.8, 174.5, 119.6, 115.2,101.9, 101.8, 100.6, 94.2, 74.2, 73.6, 71.1, 70.1, 69.9, 69.4, 69.2,68.8, 66.5, 55.9, 53.5, 48.9, 22.3, 22.0.

Synthesis of 148

Compound 148 is prepared from compound 145 following general procedureL: 40 mg, 14.18 μmol, 90% yield; R_(f)=0.15 (EtOAc:EtOH:water, 2:1:1);HRMS (ESI) calcd for C77H113N5O87S10 C₇₇H₁₀₂N₅O₈₇S₁₀Na₁₁ (M−4H)⁴⁻ m/z764.7374, found 764.7418. ¹H-NMR (500 MHz, D₂O) 7.18 (d, J=8.3 Hz, 2H),7.06 (d, J=8.3 Hz, 2H), 5.69 (d, J=3.4 Hz, 1H), 5.18 (bd, 1H), 5.15 (bd,1H), 4.91 (bd, 1H), 4.76 (d, J=3.8 Hz, 1H), 4.73-4.69 (m, 5H), 4.68 (d,J=3.8 Hz, 1H), 4.36-4.25 (m, 8H), 4.25 (d, J=11.4 Hz, 1H), 4.12-4.09 (m,3H), 4.07-3.99 (m, 16H), 3.99-3.94 (m, 6H), 3.83-3.80 (m, 3H), 3.81 (s,3H), 3.80-3.71 (m, 12H), 3.71-3.66 (m, 6H), 3.58-3.52 (m, 4H), 3.57-3.55(m, 3H), 3.54-3.53 (m, 3H), 2.05 (s, 15H); ¹³C-NMR (125 MHz, D₂O) δ175.4, 174.8, 154.8, 119.7, 115.2, 101.9, 99.3, 99.2, 99.1, 93.7, 93.6,73.8, 71.1, 70.1, 69.4, 67.9, 66.5, 69.2, 69.1, 68.7, 68.6, 55.9, 53.5,22.3.

Synthesis of 149

Compound 149 is prepared from compound 146 following general procedureL: 25 mg, 7.44 μmol, 84% yield; R_(f)=0.15 (EtOAc:EtOH:water, 2:1:1);HRMS (ESI) calcd for C₉₁H₁₂₁N₆O₁₀₄S₁₂Na₁₃ (M−5H)⁵⁻ m/z 728.1862, found728.1872. ¹H-NMR (500 MHz, D₂O) 7.18 (d, J=9.0 Hz, 2H), 7.07 (d, J=9.0Hz, 2H), 5.71 (d, J=3.4 Hz, 1H), 5.22-5.17 (m, 2H), 5.17-5.12 (m, 3H),5.07-5.03 (m, 3H), 5.01 (bd, 1H), 4.88 (bd, 1H), 4.76-4.75 (m, 2H),4.75-4.69 (m, 5H), 4.68-4.65 (m, 2H), 4.50-4.47 (m, 1H), 4.50-4.47 (m,1H), 4.36-4.32 (m, 3H), 4.32-4.29 (m, 4H), 4.36-4.32 (m, 3H), 4.29-4.25(m, 5H), 4.25-4.21 (m, 2H), 4.16-4.12 (m, 1H), 4.10-4.06 (m, 8H),4.06-4.0 (m, 10H), 4.0-3.93 (m, 8H), 3.93-3.88 (m, 4H), 3.82 (s, 3H),3.80-3.72 (m, 10H), 3.72-3.70 (m, 2H), 3.68-3.66 (m, 2H), 3.66-3.64 (m,2H), 3.59-3.56 (m, 1H), 3.56-3.55 (m, 1H), 3.54-3.53 (m, 1H), 3.52-3.50(m, 1H), 2.06 (s, 18H); ¹³C-NMR (125 MHz, D₂O) δ 174.9, 174.0, 119.6,115.2, 99.9, 99.6, 99.3, 98.8, 98.7, 94.6, 94.5, 94.0, 76.5, 73.9, 71.5,71.2, 70.3, 69.9, 69.8, 69.6, 69.3, 67.5, 66.5, 64.5, 55.9, 53.4, 22.3.

Synthesis of 91

Compound 91 is prepared from compound 83 following general procedure L:8 mg, 90%, R_(f)=0.05 (EtOAc/ethanol/water 2:2:1). ¹³C-NMR (125 MHz,D₂O, HSQC) δ 118.6, 115.0, 99.9, 99.8, 97.5, 97.1, 80.4, 80.0, 78.0,77.6, 77.5, 76.8, 76.4, 76.3, 75.4, 74.8, 70.5, 70.0, 69.6, 69.1, 69.0,68.8, 68.5, 66.3, 65.8, 61.2, 61.1, 55.7, 53.2, 22.0

Synthesis of 92

Compound 92 is prepared from compound 81 following general procedures Jfollowed by L: 6 mg, quant. R_(f)=0.05 (EtOAc/ethanol/water 2:2:1).¹³C-NMR (125 MHz, D₂O) δ 174.8, 174.6, 174.4, 174.3, 155.8, 142.3,118.7, 115.1, 100.0, 99.9, 97.5, 97.2, 97.1, 96.9, 96.8, 80.0, 77.8,77.5, 76.5, 76.1, 75.9, 75.5, 75.3, 70.7, 69.1, 68.8, 68.7, 68.6, 65.8,55.9, 53.3, 22.0

Synthesis of 93

Compound 93 is prepared from compounds 30 and 22 following generalprocedure E.

¹H NMR; (CDCl₃) δ 8.15-8.03 (m, 6H), 7.75-7.05 (m, 47H), 7.03 (d, J=9.2Hz, 2H), 6.83 (d, J=9.2 Hz, 2H), 5.61 (s, 1H), 5.46 (d, J=4.2 Hz, 1H),5.37-5.34 (m, 2H), 5.11, (t, J=4.2 Hz, 1H), 5.02 (d, J=4.0 Hz, 1H), 4.99(d, J=11.7 Hz, 1H), 4.92-3.50 (m, 56H), 3.34 (dd, J=10.1, 3.9 Hz, 1H),3.27 (dd, J=10.1, 3.9 Hz, 1H), 3.22 (dd, J=9.9, 3.9 Hz, 1H), 2.01, 1.99,1.97 (s, 3H each). ¹³C NMR; δ 170.6, 170.4, 166.9, 166.7, 166.6, 165.7,165.4, 164.9, 155.2, 154.1, 150.2, 143.2, 143.0, 141.3, 138.2, 137.7,137.6, 137.3,137.1, 137.1, 133.7, 133.5, 133.4, 129.9, 129.7, 129.4,129.0, 128.8, 128.7, 128.7, 128.4, 128.3, 128.2, 128.2, 128.1, 128.0,127.9, 127.6, 127.3, 127.2, 125.3, 125.1, 124.9, 120.1, 118.3, 114.6,100.9, 98.6, 98.2, 97.8, 97.7, 97.5, 82.7, 79.5, 78.9, 78.1, 77.7, 77.5,75.5, 75.3, 75.2, 74.9, 74.7, 74.6, 74.1, 73.6, 72.4, 72.3, 72.1, 70.4,70.3, 69.9, 68.8, 68.3, 67.6, 65.7, 65.0, 64.9, 63.8, 63.2, 63.2, 62.6,62.2, 61.9, 61.8, 55.7, 46.7, 40.6, 40.5, 40.4, 20.7.

Synthesis of 94

Compound 94 is prepared from compound 93 following general procedure D.

¹H NMR; (CDCl₃) δ 8.15-8.03 (m, 6H), 7.59-7.05 (m, 39H), 7.03 (d, J=9.3Hz, 2H), 6.84 (d, J=9.3 Hz, 2H), 5.61 (s, 1H), 5.44 (d, J=3.9 Hz, 1H),5.36-5.32 (m, 2H), 5.10 (t, J=4.5 Hz, 1H), 5.02 (d, J=4.1 Hz, 1H), 4.98(d, J=11.7 Hz, 1H), 4.93-4.36 (m, 16H), 4.31-3.38 (m, 37H), 3.29-3.20(m, 3H), 2.97 (s, 1H), 2.06, 1.98, 1.96 (s, 3H each). ¹³C NMR; 171.9,170.6, 170.5, 166.9, 166.7, 166.6, 165.7, 165.4, 165.0, 155.2, 150.2,138.3, 137.8, 137.7, 137.6, 137.3, 137.2, 133.7, 133.5, 133.4, 129.9,129.7, 129.4, 129.0, 128.8, 128.7, 128.7, 128.4, 128.4, 128.4, 128.3,128.2, 128.2, 128.1, 128.1, 128.0, 127.9, 127.8, 127.6, 127.4, 127.2,118.3, 114.6, 100.9, 98.6, 98.4, 98.2, 97.7, 97.5, 82.8, 79.2, 78.9,78.0, 77.8, 75.5, 75.4, 75.0, 74.9, 74.7, 74.6, 74.1, 73.5, 72.4, 72.4,72.1, 71.4, 70.6, 70.4, 70.3, 69.9, 68.3, 67.6, 65.7, 64.9, 64.9, 63.8,63.3, 63.2, 62.7, 62.6, 62.2, 61.9, 55.7, 40.6, 40.5, 40.4, 20.8, 20.7.

Synthesis of 95

Compound 95 is prepared from compounds 94 and 23 following generalprocedure E.

¹H NMR; (CDCl₃) δ 8.15-8.04 (m, 8H), 7.58-7.05 (m, 57H), 7.03 (d, J=9.3Hz, 2H), 6.83 (d, J=9.3 Hz, 2H), 5.61 (s, 1H), 5.45 (d, J=4.2 Hz, 1H),5.37-5.34 (m, 3H), 5.27 (t, J=8.2 Hz, 1H), 5.11-5.05 (m, 2H), 5.00-4.95(m, 2H), 4.91-4.53 (m, 18H), 4.48 (d, J=10.1 Hz, 1H), 4.42 (dd, J=11.5,8.1 Hz, 1H), 4.34-3.48 (m, 51H), 3.32-3.18 (m, 4H), 2.00, 1.99, 1.98,1.95 (s, 3H each). ¹³C NMR; δ 170.6, 170.5, 170.4, 166.9, 166.7, 166.6,166.4, 165.7, 165.4, 165.0, 164.9, 155.2, 150.2, 138.2, 137.7, 137.6,137.5, 137.3, 137.3, 133.7, 133.5, 133.4, 130.0, 129.9, 129.7, 129.4,129.0, 128.9, 128.8, 128.7, 128.6, 128.6, 128.5, 128.4, 128.4, 128.3,128.3, 128.2, 128.1, 128.1, 127.9, 127.8, 127.6, 127.5, 127.4, 127.4,127.3, 118.3, 114.6, 100.9, 100.8, 98.5, 98.3, 98.1, 97.8, 97.7, 97.5,82.8, 80.1, 78.9, 77.9, 77.9, 77.8, 77.7, 77.6, 75.6, 75.5, 75.2, 75.1,74.9, 74.8, 74.7, 74.6, 74.2, 73.6, 72.4, 72.3, 72.1, 70.4, 69.9, 69.8,68.3, 67.8, 65.7, 65.0, 64.9, 64.5, 63.8, 63.2, 63.2, 63.1, 62.7, 62.4,62.2, 61.8, 55.7, 40.7, 40.6, 40.5, 40.3, 20.8, 20.7.

Synthesis of 96

Compound 96 is prepared from compound 95 following general procedure F.

¹H NMR; (CDCl₃) δ 8.14-8.04 (m, 8H), 7.58-7.09 (m, 57H), 7.06 (d, J=9.2Hz, 2H), 6.83 (d, J=9.2 Hz, 2H), 5.63 (s, 1H), 5.52 (d, J=4.2 Hz, 1H),5.42 (d, J=4.1 Hz, 1H), 5.35 (s, 1H), 5.32 (t, J=8.6 Hz, 1H), 5.26 (t,J=8.5 Hz, 1H), 5.09 (t, J=2.9 Hz, 1H), 5.04-4.98 (m, 3H), 4.86-3.46 (m,60H), 3.32-3.24(m,9H), 3.07 (br s, 1H), 2.95 (br s, 1H), 2.00, 1.99,1.98, 1.97 (s, 3H each). ¹³C NMR; δ 170.6, 170.45, 170.40, 165.78,165.66, 165.05, 164.94, 155.25, 150.38, 138.14, 137.72, 137.60, 137.49,137.37, 133.60, 133.48, 133.28, 129.91, 129.83, 129.55, 129.11, 129.08,128.74, 128.67, 128.57, 128.45, 128.41,128.35, 128.24, 128.15, 128.07,128.04, 127.95, 127.82, 127.74, 127.62, 127.10, 126.95, 118.34, 114.70,101.06, 98.09, 98.03, 97.90, 97.63, 97.32, 83.54, 80.28, 79.30, 78.32,77.99, 77.79, 77.73, 77.64, 75.56, 75.21, 75.14, 74.97, 74.85, 74.54,74.44, 74.35, 74.17, 73.58, 73.46, 73.39, 72.90, 72.29, 72.11, 70.42,69.99, 69.60, 69.52, 69.15, 68.89, 67.93, 67.85, 64.08, 63.35, 63.25,62.86, 62.68, 62.01, 61.81, 61.61, 61.41, 60.92, 55.66, 20.81, 20.76,20.70.

Synthesis of 97

Compound 97 is prepared from compound 96 following general procedure G2.

¹H NMR; (CDCl₃) δ 8.12-8.02, (m, 8H), 7.61-7.04 (m, 57H), 7.01 (d, J=9.1Hz, 2H), 6.80 (d, J=9.1 Hz, 2H), 5.69 (s, 1H), 5.46 (d, J=6.3 Hz, 1H),5.43-5.38 (m, 5H), 5.34 (dd, J=8.7, 8.1 Hz, 1H), 5.30 (t, J=2.1 Hz, 1H),5.17-5.14 (m, 2H), 4.98-4.54 (m, 19H), 4.43 (d, J=10.5 Hz, 1H), 4.37 (d,J=10.9 Hz, 1H), 4.31-4.08 (m, 11H), 4.05 (t, J=2.8 Hz, 1H), 4.01 (t,J=7.2 Hz, 1H), 3.94-3.65 (m, 16H), 3.59-3.42 (m, 12H), 3.34-3.30 (m,2H), 3.24-3.17 (m, 3H), 2.97 (s, 3H), 2.09, 2.07, 2.01, 2.00 (s, 3Heach). ¹³C NMR; δ 170.75, 170.61, 170.38, 169.67, 169.16, 167.70,167.50, 165.62, 165.10, 164.66, 155.25, 150.49, 138.12, 137.86, 137.57,137.52, 137.40, 137.17, 137.07, 133.92, 133.73, 133.64, 133.53, 129.97,129.90, 129.71, 129.47, 129.13, 129.05, 128.94, 128.86, 128.80, 128.76,128.55, 128.41, 128.33, 128.24, 128.16, 128.06, 128.03, 127.93, 127.77,127.63, 127.51, 127.46, 125.32, 117.97, 114.66, 101.15, 101.08, 98.89,98.58, 98.17, 97.83, 97.67, 97.22, 82.81, 82.56, 80.22, 78.31, 77.80,77.64, 77.51, 77.48, 76.05, 75.58, 75.45, 75.37, 75.28, 75.01, 74.96,74.86, 74.81, 74.60, 74.35, 73.68, 73.51, 72.86, 72.47, 72.09, 71.45,69.85, 69.78, 69.38, 69.08, 68.10, 63.41, 63.32, 62.82, 62.73, 62.20,61.57, 61.42, 55.66, 52.72, 52.08, 51.96, 51.75, 20.87, 20.81.

Synthesis of 98

Compound 98 is prepared from compound 97 following general procedure H.

¹H NMR; (CDCl₃) δ 8.07-7.99 (m, 8H), 7.60-7.41 (m, 12H), 7.35-6.98 (m,47H), 6.79 (d, J=9.1 Hz, 2H), 5.79 (d, J=9.6 Hz, 1H), 5.72 (d, J=9.6 Hz,1H), 5.65 (d, J=1.6 Hz, 1H), 5.54 (d, J=9.5 Hz, 1H), 5.42 (t, J=8.4 Hz,1H), 5.39-5.29 (m, 3H), 5.15 (t, J=5.4 Hz, 1H), 4.99-4.96 (m, 2H),4.94-4.91 (m, 3H), 4.88-3.90 (m, 44H), 3.86-3.59 (m, 9H), 3.74 (s, 3H),3.57-3.47 (m, 2H), 3.55, 3.54 (s, 3H each), 3.38-3.32 (m, 1H), 3.36,3.24, 2.10, 2.01, 1.97, 1.91, 1.40, 1.39, 1.38, 1.31 (s, 3H each). ¹³CNMR; δ 171.11, 170.70, 170.64, 170.58, 170.32, 170.12, 170.02, 169.28,169.01, 167.41, 167.20, 165.59, 165.31, 164.87, 164.67, 155.39, 150.41,138.72, 138.45, 138.12, 137.85, 137.70, 137.03, 136.81, 136.38, 136.32,133.97, 133.87, 133.81, 129.73, 129.04, 128.98, 128.85, 128.72, 128.62,128.55, 128.49, 128.32, 128.24, 128.12, 128.09, 128.02, 127.95, 127.78,127.72, 127.60, 127.50, 127.41, 127.36, 127.30, 127.23, 127.02, 125.31,118.07, 117.81, 114.68, 101.32, 101.12, 99.50, 98.72, 98.08, 97.81,97.57, 81.57, 81.40, 80.50, 78.10, 77.89, 77.82, 76.75, 75.42, 75.27,75.18, 75.02, 74.95, 74.87, 74.73, 74.34, 73.76, 73.55, 72.91, 72.70,72.56, 71.86, 70.86, 70.70, 70.20, 70.10, 69.77, 68.77, 68.33, 62.19,61.67, 61.53, 61.38, 55.64, 52.82, 52.52, 52.48, 52.09, 51.97, 51.91,51.78, 22.76, 22.64, 21.45, 20.98, 20.79, 20.76, 20.71.

Synthesis of 99

Compound 99 is prepared from compound 98 following general procedure I.

¹H NMR; (CDCl₃) δ 8.03-7.92 (m, 8H), 7.58-7.40 (m, 12H), 7.35-6.95 (m,47H), 6.78 (d, J=9.1 Hz, 2H), 5.75 (d, J=9.0 Hz, 1H), 5.69 (d, J=9.5 Hz,1H), 5.63 (d, J=2.0 Hz, 1H), 5.52 (d, J=9.1 Hz, 1H), 5.43 (t, J=8.3 Hz,1H), 5.37-5.32 (m, 3H), 5.28 (d, J=8.5 Hz, 1H), 5.19 (t, J=4.5 Hz, 1H),5.07 (d, J=3.5 Hz, 1H), 5.00-4.77 (m, 10 H), 4.71-4.45 (m, 11H), 4.32(d, J=12.2 Hz, 1H), 4.22 (dt, J=10.0, 3.6 Hz, 1H), 4.17-3.19 (m, 36H),3.74, 3.56, 3.54, 3.24, 3.23, 1.47, 1.45, 1.43, 1.33 (s, 3H each). ¹³CNMR; δ 170.58, 170.19, 170.09, 170.04, 169.09, 169.05, 167.93, 165.55,165.38, 165.05, 164.74, 155.39, 150.46, 138.97, 138.92, 138.50, 138.29,137.93, 137.06, 136.95, 136.54, 133.98, 133.86, 129.75, 129.60, 129.06,128.97, 128.88, 128.61, 128.57, 128.52, 128.48, 128.31, 128.23, 128.11,127.98, 127.88, 127.82,127.7, 127.41, 127.24, 118.07, 114.68, 100.64,100.56, 98.96, 98.36, 98.27, 98.15, 97.74, 97.04, 81.41, 81.28, 80.06,77.77, 77.54, 77.27, 76.34, 75.50, 75.16, 75.09, 74.98, 74.78, 74.68,74.44, 74.07, 73.93, 73.72, 73.34, 73.06, 72.91, 72.79, 72.63, 72.49,72.39, 71.94, 71.44, 70.55, 68.79, 68.48, 61.60, 60.46, 60.40, 60.10,59.96, 55.66, 52.81, 52.64, 52.32, 52.07, 51.77, 22.66.

Synthesis of 100

Compound 100 is prepared from compound 99 following general procedures Jand then K.

¹H NMR; (MeOD) δ 7.44-7.17 (m, 45H), 7.09 (d, J=9.1 Hz, 2H), 6.84 (d,J=9.1 Hz, 2H), 5.49 (s, 1H), 5.43 (m, 2H), 5.27 (s, 1H), 5.12-4.53 (m,32H), 4.44-3.51 (m, 34H), 3.73 (s, 3H), 1.86, 1.84, 1.78, 1.66 (s, 3Heach). ¹³C NMR; δ 175.40, 175.31, 174.45, 173.33, 173.25, 173.18,173.11, 168.34, 156.54, 152.41, 140.30, 140.21, 140.04, 139.85, 139.80,139.45, 139.21, 133.67, 130.69, 129.75, 129.60, 129.49, 129.41, 129.35,129.29, 129.01, 128.89, 128.69, 128.60, 128.51, 128.47, 128.21, 119.28,115.72, 103.97, 103.91, 101.99, 101.73, 98.75, 98.22, 97.35, 86.11,85.74, 81.96, 80.94, 80.50, 80.22, 79.28, 77.93, 77.82, 77.68, 77.56,76.67, 76.47, 76.30, 76.20, 75.97, 75.83, 75.28, 75.16, 75.09, 74.06,73.63, 73.15, 72.90, 71.64, 71.40, 71.09, 70.11, 69.31, 68.42, 67.47,67.30, 67.06, 56.19, 54.38, 53.56, 53.47, 23.00.

Synthesis of 101

Compound 101 is prepared from compound 100 following general procedureL.

¹H NMR; (D₂O) δ 7.13 (d, J=8.8 Hz, 2H), 6.98 (d, J=8.8 Hz, 2H), 5.46 (s,1H), 5.41 (m, 2H), 5.16 (m, 2H), 4.98 (s, 1H), 4.79-4.68 (m, 4H), 4.57(m, 2H), 4.44 (m, 2H), 4.36-4.33 (m, 2H), 4.23-4.15 (m, 4H), 4.11 (s,1H), 4.07-3.69 (m, 24H), 3.80 (s, 3H), 3.56 (t, J=9.6 Hz, 1H), 3.36-3.32(m, 2H), 2.04, 2.03 (s, 3H each), 2.01 (s, 6H). ¹³C NMR δ 174.97,174.89, 174.67, 174.52, 174.43, 154.81, 150.34, 119.34, 115.18, 102.00,101.96, 100.69, 97.08, 96.84, 94.76, 94.39, 77.37, 77.26, 76.90, 76.51,76.28, 76.20, 74.34, 73.92, 73.57, 70.66, 70.12, 69.95, 69.59, 69.38,69.21, 69.17, 69.08, 69.01, 68.85, 68.11, 66.41, 66.26, 65.85, 55.91,53.67, 53.60, 53.14, 53.04, 22.04, 22.01.

Synthesis of 102

Compound 102 is prepared from compounds 125 and 24 following generalprocedure E.

¹H NMR; (CDCl₃) δ 8.11-8.05 (m, 6H), 7.76 (m, 2H), 7.60-7.17 (m, 43H),7.08-7.06 (m, 2H), 6.88 (d, J=9.1 Hz, 2H), 6.76 (d, J=9.1 Hz, 2H),5.54-5.51 (m, 2H), 5.18-5.12 (m, 4H), 5.07 (d, J=7.1 Hz, 1H), 4.96 (d,J=10.4 Hz, 1H), 4.86-4.67 (m, 10H), 4.59 (dd, J=11.8, 2.6 Hz, 1H),4.51-4.45 (m, 3H), 4.39-3.61 (m, 55H), 3.74 (s, 3H), 3.33-3.27 (m, 3H),2.04, 2.03, 2.00 (s, 3H each). ¹³C NMR; δ 170.57, 170.52, 170.46,166.82, 166.76, 165.51, 165.45, 165.08, 155.70, 154.17, 150.99, 143.20,143.05, 141.34, 137.85, 137.72, 137.35, 137.24, 137.13, 137.06, 133.54,133.47, 129.82, 129.52, 129.38, 128.75, 128.67, 128.59, 128.48, 128.44,128.40, 128.30, 128.26, 128.19, 128.10, 128.02, 127.99, 127.87, 127.79,127.67, 127.26, 125.03, 124.84, 120.14, 118.77, 114.56, 100.11, 98.81,98.14, 97.98, 97.94, 97.79, 82.75, 78.84, 78.52, 77.92, 75.59, 75.28,75.08, 75.01, 74.58, 74.53, 74.29, 74.21, 74.13, 73.87, 73.63, 73.54,73.38, 72.54, 70.45, 70.32, 70.22, 69.80, 68.83, 67.73, 67.12, 64.60,63.77, 63.68, 63.61, 63.28, 63.12, 62.19, 61.93, 55.65, 46.75, 40.64,40.53, 20.77, 20.73, 20.63.

Synthesis of 103

Compound 103 is prepared from compound 102 following general procedureD.

¹H NMR; (CDCl₃) δ 8.12-8.05 (m, 6H), 7.57 (t, J=7.4 Hz, 1H), 7.53-7.48(m, 2H), 7.46-7.40 (m, 6H), 7.34-7.19 (m, 30H), 6.88 (d, J=9.1 Hz, 2H),6.76 (d, J=9.1 Hz, 2H), 5.54-5.51 (m, 2H), 5.18-5.14 (m, 2H), 5.12-5.10(m, 2H), 5.07 (d, J=7.1 Hz, 1H), 4.95 (d, J=10.5 Hz, 1H), 4.86-4.67 (m,10H), 4.61-4.55 (m, 2H), 4.51-4.44 (m, 3H), 4.41 (d, J=7.8 Hz, 1H),4.37-4.19 (m, 8H), 4.15-3.98 (m, 8H), 3.94 (s, 2H), 3.91 (s, 2H), 3.89(s, 2H), 3.91-3.69 (m, 8H), 3.74 (s, 3H), 3.63-3.55 (m, 2H), 3.40-3.27(m, 3H), 3.22 (dd, J=10.1, 3.6 Hz, 1H), 2.04 (s, 6H), 2.03, 2.02 (s, 3Heach). ¹³C NMR; δ 171.70, 170.70, 170.58, 167.02, 166.79, 166.75,165.51, 165.08, 155.68, 150.98, 137.84, 137.74, 137.69, 137.34, 137.24,137.20, 133.52, 133.47, 129.87, 129.81, 129.50, 129.37, 128.69, 128.58,128.42, 128.40, 128.31, 128.24, 128.16, 128.10, 127.97, 127.78, 127.66,118.76, 114.55, 100.11, 98.95, 98.23, 97.91, 97.79, 82.74, 79.72, 78.71,78.50, 75.57, 75.38, 75.27, 75.19, 75.12, 74.65, 74.57, 74.28, 74.23,73.62, 73.52, 73.43, 72.53, 71.29, 70.56, 70.48, 70.38, 70.31, 70.23,67.76, 67.68, 64.59, 63.59, 63.27, 63.08, 62.80, 62.17, 60.39, 55.64,40.66, 40.53, 20.74.

Synthesis of 104

Compound 104 is prepared from compounds 103 and 23 following generalprocedure E.

¹H NMR; (CDCl₃) δ 8.08-8.00 (m, 8H), 7.58-7.12 (m, 57H), 6.88 (d, J=9.1Hz, 2H), 6.76 (d, J=9.1 Hz, 2H), 5.54-5.51 (m, 2H), 5.43 (d, J=3.8 Hz,1H), 5.35 (t, J=8.2 Hz, 1H), 5.16 (t, J=4.3 Hz, 1H), 5.12-5.09 (m, 2H),5.07 (d, J=7.1 Hz, 1H), 5.03 (d, J=3.8 Hz, 1H), 4.94 (d, J=10.4 Hz, 1H),4.91-4.54 (m, 14H), 4.44 (dd, J=10.4, 7.6 Hz, 1H), 4.34-3.55 (m, 41H),3.93, 3.89, 3.81, 3.80 (s, 2H each), 3.73 (s, 3H), 3.49 (t, J=9.4 Hz,1H), 3.32-3.20 (m, 4H), 2.03, 2.00, 1.99, 1.96 (s, 3H each). ¹³C NMR; δ170.58, 170.52, 170.43, 166.82, 166.79, 166.75, 166.60, 165.48, 165.43,165.09, 164.94, 155.70, 150.99, 138.19, 137.84, 137.72, 137.51, 137.35,137.25, 137.18, 133.70, 133.47, 129.83, 129.51, 129.36, 129.06, 128.80,128.75, 128.68, 128.62, 128.57, 128.40, 128.29, 128.25, 128.19, 128.12,128.04, 127.98, 127.79, 127.68, 127.56, 127.21, 125.33, 118.77, 114.56,100.95, 100.11, 98.57, 98.20, 98.00, 97.91, 97.81, 82.74, 80.13, 78.66,78.49, 78.06, 77.90, 77.75, 75.64, 75.57, 75.45, 75.23, 75.09, 74.87,74.77, 74.60, 74.43, 74.22, 74.11, 73.62, 73.56, 72.54, 72.32, 70.49,70.31, 69.89, 67.81, 67.62, 65.02, 64.58, 63.57, 63.50, 63.21, 62.39,62.16, 61.88, 55.65, 40.65, 40.60, 40.53, 40.45, 21.46, 20.78, 20.70.

Synthesis of 105

Compound 105 is prepared from compound 104 following general procedureF.

¹H NMR; (CDCl₃) δ 8.10-8.00 (m, 8H), 7.58-7.49 (m, 3H), 7.46-7.12 (m,54H), 6.89 (d, J=9.0 Hz, 2H), 6.76 (d, J=9.0 Hz, 2H), 5.65 (s, 1H), 5.54(t, J=8.0 Hz, 1H), 5.50 (s, 1H), 5.31 (t, J=8.1 Hz, 1H), 5.17 (s, 1H),5.12-5.08 (m, 3H), 4.99 (s, 1H), 4.89-4.63 (m, 12H), 4.58-4.53 (m, 3H),4.47-4.43 (m, 2H), 4.35-3.42 (m, 40H), 3.72 (s, 3H), 3.35-3.24 (m, 6H),3.16-3.11 (m, 1H), 3.06-3.01 (m, 1H), 2.03 (s, 3H), 1.99 (s, 6H), 1.97(s, 3H). ¹³C NMR; δ 170.58, 170.42, 165.82, 165.72, 165.10, 164.96,155.65, 151.13, 138.14, 137.88, 137.61, 137.53, 137.46, 137.34, 133.61,133.40, 129.81, 129.63, 129.06, 128.75, 128.68, 128.55, 128.45, 128.37,128.26, 128.14, 128.08, 128.03, 127.86, 127.77, 127.65, 126.86, 125.33,118.51, 114.66, 101.22, 100.53, 98.12, 97.94, 97.86, 97.62, 97.42,83.65, 83.35, 80.27, 79.21, 78.82, 78.33, 78.00, 77.78, 77.34, 77.08,76.83, 75.55, 75.14, 75.07, 74.88, 74.81, 74.46, 74.36, 74.30, 74.17,73.97, 73.42, 73.35, 73.06, 72.99, 72.79, 72.49, 70.22, 70.09, 69.96,69.62, 68.82, 68.19, 67.53, 63.98, 63.46, 63.24, 62.63, 62.43, 62.10,61.95, 61.77, 61.22, 61.02, 55.65, 21.47, 20.81.

Synthesis of 106

Compound 106 is prepared from compound 105 following general procedureG2.

¹H NMR; (CDCl₃) δ 8.12-8.01 (m, 8H), 7.58-7.52 (m, 4H), 7.48-7.41 (m,8H), 7.37-7.10 (m, 45H), 6.85 (d, J=9.1 Hz, 2H), 6.73 (d, J=9.1 Hz, 2H),5.52-5.39 (m, 6H), 5.18-5.14 (m, 2H), 5.07 (d, J=6.8 Hz, 1H), 5.03 (d,J=10.8 Hz, 1H), 4.94 (d, J=3.6 Hz, 1H), 4.91-4.86 (m, 4H), 4.82 (s, 1H),4.80 (s, 1H), 4.78-4.63 (m, 9H), 4.55 (d, J=11.0 Hz, 1H), 4.44 (d,J=10.8 Hz, 1H), 4.37-4.18 (m, 9H), 4.14-4.01 (m, 8H), 3.97-3.69 (m,11H), 3.72 (s, 3H), 3.59-3.42 (m, 5H), 3.51, 3.50, 3.43 (s, 3H each),3.34-3.21 (m, 4H), 3.26 (s, 3H), 2.09, 2.08, 2.02, 2.01 (s, 3H each).¹³C NMR; δ 170.76, 170.68, 170.60, 170.42, 169.73, 169.57, 168.14,167.70, 165.22, 165.09, 165.00, 164.69, 155.70, 150.95, 137.96, 137.89,137.76, 137.57, 137.52, 137.44, 137.39, 137.29, 137.19, 133.92, 133.81,133.63, 133.44, 129.95, 129.86, 129.80, 129.74, 129.46, 129.11, 129.05,128.86, 128.77, 128.55, 128.33, 128.25, 128.16, 128.06, 127.94, 127.85,127.80, 127.59, 125.32, 118.74, 114.50, 101.19, 100.73, 98.72, 98.66,97.91, 97.85, 97.69, 97.40, 82.49, 82.17, 80.23, 77.99, 77.74, 77.63,77.48, 76.28, 75.95, 75.58, 75.33, 75.10, 75.02, 74.93, 74.84, 74.65,74.57, 74.51, 74.37, 74.26, 73.80, 73.67, 72.28, 71.62, 71.15, 69.87,69.65, 69.45, 63.42, 62.95, 62.84, 62.19, 61.55, 55.62, 52.70, 52.22,51.85, 51.75, 20.80, 20.75.

Synthesis of 107

Compound 107 is prepared from compound 106 following general procedureH.

¹H NMR; (CDCl₃) δ 8.07-8.00 (m, 8H), 7.59-7.54 (m, 4H), 7.47-7.42 (m,6H), 7.35-7.07 (m, 47H), 6.84 (d, J=9.1 Hz, 2H), 6.73 (d, J=9.1 Hz, 2H),5.72-5.68 (m, 2H), 5.64-5.61 (m, 2H), 5.53 (dd, J=8.5, 6.6 Hz, 1H), 5.42(dd, J=9.0, 8.0 Hz, 1H), 5.33-5.30 (m, 2H), 5.20-5.15 (m, 2H), 5.06 (d,J=6.6 Hz, 1H), 5.05 (d, J=3.4, Hz, 1H), 4.96-4.88 (m, 5H), 4.84-4.47 (m,18H), 4.41-4.35 (m, 4H), 4.32-3.91 (m, 19H), 3.84-3.46 (m, 10H), 3.72,3.55, 3.49 (s, 3H each), 3.41-3.35 (m, 2H), 3.37, 3.32 (s, 3H each),2.09, 2.08, 2.01, 1.94, 1.39 (s, 3H each), 1.38 (s, 6H), 1.35 (s, 3H).¹³C NMR; δ 171.04, 170.67, 170.62. 170.21, 170.06, 169.99, 169.28,169.16, 167.69, 167.22, 165.49, 165.21, 164.99, 164.72, 155.74, 150.86,138.70, 138.47, 138.13, 137.70, 136.88, 136.77, 136.51, 136.37, 133.85,133.58, 129.76, 129.70, 129.26, 129.03, 128.95, 128.62, 128.53, 128.49,128.31, 128.23, 128.16, 128.10, 128.02, 127.90, 127.78, 127.71, 127.56,127.37, 127.29, 127.06, 125.30, 118.61, 114.51, 101.36, 100.90, 99.62,99.27, 98.02, 97.83, 81.40, 80.93, 80.52, 78.02, 77.90, 77.49, 75.75,75.45, 75.31, 74.96, 74.86, 74.67, 73.93, 73.86, 73.58, 73.21, 72.08,71.64, 71.06, 70.72, 70.65, 70.15, 69.82, 62.18, 61.52, 55.61, 52.79,52.71, 52.53, 51.76, 51.69, 22.75, 22.71, 22.61, 22.53, 20.97, 20.95,20.79, 20.73.

Synthesis of 108

Compound 108 is prepared from compound 107 following general procedureI.

¹H NMR; (CDCl₃) δ 8.04-8.00 (m, 4H), 7.96-7.92 (m, 4H), 7.60-7.54 (m,4H), 7.48-7.41 (m, 8H), 7.35-7.09 (m, 45H), 6.84 (d, J=9.1 Hz, 2H), 6.73(d, J=9.1 Hz, 2H), 5.99 (d, J=9.2 Hz, 1H), 5.91 (d, J=9.1 Hz, 1H), 5.75(d, J=9.5 Hz, 1H), 5.63 (d, J=9.3 Hz, 1H), 5.53 (dd, J=8.5, 6.8 Hz, 1H),5.45-5.39 (m, 2H), 5.34 (d, J=4.8 Hz, 1H), 5.21 (t, J=6.0 Hz, 1H), 5.14(br s, 1H), 5.12 (d, J=3.5 Hz, 1H), 5.07 (d, J=6.7 Hz, 1H), 4.99 (d,J=3.5 Hz, 1H), 4.96-4.90 (m, 3H), 4.83-4.73 (m, 5H), 4.68-4.49 (m, 12H),4.37-4.34 (m, 2H), 4.28-4.20 (m, 4H), 4.14-3.85 (m, 16H), 3.73-3.16 (m,15H), 3.71, 3.58, 3.49, 3.35, 3.20, 1.46, 1.44, 1.44, 1.41 (s, 3H each).¹³C NMR δ 170.72, 170.53, 170.27, 170.12, 169.15, 169.09, 167.97,167.91, 165.55, 165.41, 165.02, 164.78, 155.73, 150.85, 138.96, 138.50,138.45, 138.29, 137.94, 137.00, 136.87, 136.54, 133.85, 133.59, 129.74,129.65,129.55, 129.23, 128.98, 128.85, 128.59, 128.53, 128.34, 128.25,128.14, 127.97, 127.92, 127.83, 127.78, 127.59, 127.37, 127.22, 127.16,118.61, 114.52, 100.88, 100.75, 98.92, 97.63, 96.87, 96.66, 81.34,81.07, 80.09, 77.71, 77.57, 76.75, 76.39, 76.30, 76.26, 75.43, 75.36,75.19, 75.00, 74.76, 74.66, 74.31, 73.93, 73.77, 73.63, 73.33, 73.10,72.94, 72.39, 71.98, 71.27, 71.10, 70.23, 67.19, 67.14, 66.53, 66.27,66.19, 61.57, 60.51, 60.33, 59.91, 55.60, 52.73, 52.64, 52.12, 51.83,51.76, 22.67, 22.62.

Synthesis of 109

Compound 109 is prepared from compound 108 following general procedureJ.

¹H NMR; (CD₃OD) δ 8.22 (d, J=7.3 Hz, 2H), 8.12-8.09 (m, 4H), 8.04 (d,J=7.3 Hz, 2H), 7.65-7.43 (m, 12H), 7.35-7.01 (m, 43H), 6.97-6.95 (m,2H), 6.85 (d, J=9.1 Hz, 2H), 6.75 (d, J=9.1 Hz, 2H), 5.58 (d, J=3.7 Hz,1H), 5.53 (d, J=4.6 Hz, 1H), 5.43-5.35 (m, 4H), 5.28-5.26 (m, 2H), 5.23(t, J=4.7 Hz, 1H), 5.17 (t, J=5.5 Hz, 1H), 5.04 (d, J=3.2 Hz, 1H), 5.01(d, J=11.0 Hz, 1H), 4.97 (d, J=3.4 Hz, 1H), 4.86-4.14 (m, 35H),4.09-3.90 (m, 8H), 3.74-3.48 (m, 7H), 3.63, 3.56, 3.50 (s, 3H each),3.44-3.39 (m, 3H), 3.19, 2.98, 1.85, 1.77, 1.55, 1.47 (s, 3H each). ¹³CNMR; (CD₃OD) δ 173.53, 173.33, 173.24, 170.78, 170.49, 170.43, 170.38,167.43, 167.26, 166.86, 166.56, 157.24, 152.36, 140.26, 140.07, 139.87,139.82, 138.79, 138.67, 138.49, 135.11, 134.84, 131.23, 130.86, 130.61,130.16, 130.04, 129.95, 129.86, 129.58, 129.51, 129.44, 129.36, 129.31,129.28, 129.22, 129.11, 129.04, 128.93, 128.84, 128.59, 128.40, 128.25,128.14, 119.51, 115.73, 101.70, 99.18, 99.08, 98.95, 97.45, 97.01,83.95, 83.43, 81.72, 79.90, 79.60, 79.36, 78.96, 78.19, 76.87, 76.22,75.87, 75.65, 75.41, 75.31, 75.14, 74.98, 74.79, 74.59, 74.46, 73.90,72.82, 72.27, 71.79, 71.42, 71.13, 70.63, 66.83, 66.21, 65.74, 56.14,54.07, 53.85, 53.66, 53.51, 53.33, 52.82, 52.58, 22.93, 22.84, 22.80.

Synthesis of 110

Compound 110 is prepared from compound 109 following general procedureK.

¹H NMR; (CD₃OD) δ 7.39-7.18 (m, 45H), 7.04 (d, J=9.1 Hz, 2H), 6.83 (d,J=9.1 Hz, 2H), 5.42-5.40 (m, 2H), 5.23 (br s, 2H), 5.11-5.07 (m, 2H),5.01-4.54 (m, 25H), 4.47-3.51 (m, 35H), 3.74, 1.86, 1.77, 1.69, 1.62 (s,3H each). ¹³C NMR; (CD₃OD) δ 175.75, 175.05, 173.29, 173.12, 173.00,156.89, 153.22, 140.26, 139.98, 139.86, 139.73, 139.33, 139.19, 129.76,129.60, 129.54, 129.49, 129.40, 129.32, 129.03, 128.86, 128.80, 128.63,128.58, 119.55, 115.57, 103.94, 103.85, 102.28, 102.09, 98.82, 98.63,98.03, 97.13, 86.19, 85.83, 81.96, 80.96, 80.84, 80.48, 79.34, 78.33,78.04, 77.62, 76.62, 76.30, 75.95, 75.85, 75.65, 75.43, 75.16, 74.78,73.99, 73.15, 71.69, 71.46, 71.35, 70.59, 70.18, 69.39, 67.41, 67.08,56.16, 54.41, 54.30, 53.60, 23.00.

Synthesis of 111

Compound 111 is prepared from compound 110 following general procedureL.

¹H NMR; (D₂O) δ 7.10 (d, J=8.3 Hz, 2H), 6.97 (d, J=8.3 Hz, 2H),5.42-5.39 (m, 2H), 5.15 (br s, 2H), 4.98-4.96 (m, 3H), 4.76-4.74 (m, 2Hand HOD), 4.57 (d, J=7.8 Hz, 1H), 4.45 (d, J=10.8 Hz, 1H), 4.36-4.31 (m,3H), 4.22-4.14 (m, 4H), 4.08-3.69 (m, 27H), 3.58-3.55 (m, 2H), 3.36-3.32(m, 1H), 2.04, 2.00 (s, 6H each). ¹³C NMR δ 175.05, 174.95, 174.67,174.52, 174.42, 154.84, 151.02, 118.38, 115.13, 102.01, 101.96, 101.91,101.29, 97.17, 97.05, 94.48, 94.35, 77.25, 77.11, 76.92, 76.80, 76.70,76.62, 76.44, 76.30, 76.20, 74.40, 74.22, 73.53, 73.35, 70.66, 70.10,69.96, 69.60, 69.55, 69.41, 69.35, 69.31, 69.23, 69.13, 68.95, 68.79,66.38, 66.23, 65.88, 55.90, 53.76, 53.65, 53.59, 53.04, 22.00.

Synthesis of 112

Compound 112 is prepared from compounds 26 and 22 following generalprocedure E.

¹H NMR; (CDCl₃) δ 8.13-8.08 (m, 4H), 7.76-7.73 (m, 2H), 7.60-7.53 (m,4H), 7.49-7.33 (m, 10H), 7.30-7.13 (m, 18H), 7.01 (d, J=9.1 Hz, 2H),6.83 (d, J=9.1 Hz, 2H), 5.57 (s, 1H), 5.48 (d, J=3.9 Hz, 1H), 5.36 (t,J=8.3 Hz, 1H), 5.33 (t, J=1.6 Hz, 1H), 4.97 (d, J=11.7 Hz, 1H), 4.86 (t,J=9.5 Hz, 1H), 4.78-4.69 (m, 4H), 4.65-4.61 (m, 2H), 4.57 (d, J=3.8 Hz,1H), 4.49-4.45 (m, 2H), 4.33-4.13 (m, 10H), 4.05-3.58 (m, 15H), 3.77 (s,3H), 3.51 (t, J=9.4 Hz, 1H), 3.35 (dd, J=10.2, 3.9 Hz, 1H), 3.25 (dd,J=10.1, 3.8 Hz, 1H), 2.02, 1.98 (s, 3H each). ¹³C NMR δ 170.55, 170.45,166.87, 166.56, 165.65, 164.93, 155.23, 154.12, 150.12, 143.25, 143.01,141.32, 138.25, 137.59, 137.19, 137.09, 133.67, 133.55, 129.89, 129.85,129.63, 129.05, 129.02, 128.81, 128.76, 128.42, 128.25, 128.12, 128.09,127.98, 127.93, 127.87, 127.57, 127.48, 127.25, 127.17, 125.32, 125.11,124.91, 120.12, 118.29, 114.56, 100.88, 98.76, 97.85, 97.51, 82.67,78.40, 77.78, 77.49, 75.43, 75.21, 74.69, 74.61, 74.57, 74.11, 72.44,72.38, 72.28, 70.40, 69.99, 68.77, 68.09, 65.60, 65.01, 64.76, 63.34,62.63, 62.15, 61.80, 55.70, 46.71, 40.44, 40.41, 20.69.

Synthesis of 113

Compound 113 is prepared from compound 112 following general procedureD.

¹NMR; (CDCl₃) δ8.13-8.08 (m, 4H), 7.57-7.52 (m, 2H), 7.49-7.13 (m, 24H),7.01 (d, J=9.1 Hz, 2H), 6.83 (d, J=9.1 Hz, 2H), 5.57 (s, 1H), 5.45 (d,J=3.9 Hz, 1H), 5.36 (t, J=8.2 Hz, 1H), 5.32 (s, 1H), 4.97 (d, J=11.6 Hz,1H), 4.89 (s, 2H), 4.80-4.68 (m, 4H), 4.60 (d, J=7.8 Hz, 1H), 4.57 (d,J=3.7 Hz, 1H), 4.51-4.45 (m, 2H), 4.26-4.10 (m, 5H), 4.06 (d, J=10.4 Hz,1H), 4.00-3.96 (m, 2H), 3.90 (d, J=11.0 Hz, 1H), 3.85-3.58 (m, 12H),3.78 (s, 3H), 3.51 (t, J=10 Hz, 1H), 3.44-3.39 (m, 1H), 3.25-3.22 (m,2H), 2.95 (d, J=4 Hz, 1H), 2.07, 1.97 (s, 3H each). ¹³C NMR δ 171.87,170.56, 166.90, 166.54, 165.64, 164.94, 155.21, 150.11, 138.29, 137.78,137.58, 137.25, 133.65, 133.54, 129.88, 129.84, 129.62, 129.03, 128.79,128.76, 128.66, 128.40, 128.20, 128.16, 128.11, 128.07, 127.97, 127.79,127.61, 127.44, 127.10, 118.27, 114.54, 100.87, 98.77, 98.25, 97.49,82.78, 79.16, 78.38, 77.81, 75.42, 75.14, 74.58, 74.16, 72.40, 71.35,70.61, 69.98, 68.05, 65.58, 64.97, 64.74, 63.32, 62.71, 62.66, 62.15,55.69, 40.43, 20.78, 20.70.

Synthesis of 114

Compound 114 is prepared from compounds 113 and 24 following generalprocedure E.

¹H NMR; (CDCl₃) δ 8.13-8.07(m, 6H), 7.78-7.75 (m, 2H), 7.60-7.53 (m,4H), 7.49-7.13 (m, 39H), 7.08-7.06 (m, 2H), 7.01 (d, J=9.1 Hz, 2H), 6.83(d, J=9.1 Hz, 2H), 5.56 (s, 1H), 5.44 (d, J=3.9 Hz, 1H), 5.36 (d, J=8.2Hz, 1H), 5.33 (bs, 1H), 5.16-5.14 (m, 2H), 4.98 (d, J=3.8 Hz, 1H), 4.96(d, J=5.1 Hz, 1H), 4.85 (d, J=11.4 Hz, 1H), 4.80-4.67 (m, 7H), 4.59 (d,J=7.9 Hz, 1H), 4.57 (d, J=3.8 Hz, 1H), 4.51-4.45 (m, 3H), 4.44-4.41 (m,1H), 4.34-4.28 (m, 2H), 4.24-4.02 (m, 15H), 3.98-3.89 (m, 6H), 3.82-3.58(m, 13H), 3.77 (s, 3H), 3.51 (t, J=9.9 Hz, 1H), 3.33-3.29 (m, 2H), 3.24(dd, J=10.1, 3.7 Hz, 1H), 2.05, 2.00, 1.98 (s, 3H each). ¹³C NMR δ170.51, 170.48, 166.84, 166.75, 166.55, 165.65, 165.47, 164.94, 155.24,154.19, 150.14, 143.22, 143.07, 141.38, 141.35, 138.28, 137.88, 137.82,137.61, 137.28, 137.21, 137.09, 133.64, 133.56, 129.90, 129.86, 129.65,129.54, 129.07, 128.92, 128.78, 128.60, 128.48, 128.43, 128.31, 128.26,128.21, 128.14, 128.09, 128.02, 127.88, 127.81, 127.72, 127.57, 127.46,127.27, 127.22, 125.34, 125.05, 124.85, 120.17, 120.15, 118.30, 114.56,100.88, 98.88, 98.81, 97.99, 97.83, 97.52, 82.80, 78.71, 78.38, 77.94,77.69, 75.45, 75.30, 75.20, 75.14, 75.02, 74.68, 74.64, 74.56, 74.44,74.19, 73.85, 73.35, 72.46, 72.38, 70.32, 70.20, 70.02, 69.77, 68.83,68.09, 67.08, 65.60, 64.87, 64.75, 63.90, 63.41, 63.34, 63.14, 62.11,62.07, 61.97, 55.70, 46.77, 40.66, 40.45, 40.43, 20.80, 20.72, 20.65.

Synthesis of 115

Compound 115 is prepared from compound 114 following general procedureD.

¹H NMR; (CDCl₃) δ 8.13-8.07 (m, 6H), 7.58-7.41 (m, 10 H), 7.34-7.12 (m,29H), 7.01 (d, J=9.1 Hz, 2H), 6.83 (d, J=9.1 Hz, 2H), 5.56 (s, 1H), 5.43(d, J=3.9 Hz, 1H), 5.36-5.32 (m, 2H), 5.15 (t, J=4 Hz, 1H), 5.11 (d,J=3.7 Hz, 1H), 4.98 (d, J=3.9 Hz, 1H), 4.96 (d, J=5.3 Hz, 1H), 4.84 (d,J=11.3 Hz, 1H), 4.79-4.66 (m, 7H), 4.60-4.45 (m, 6H), 4.41-4.37 (m, 2H),4.31 (dd, J=12.2, 3.6 Hz, 1H), 4.25-4.06 (m, 10H), 3.98-3.89 (m, 5H),3.80-3.68 (m, 11H), 3.77 (s, 3H), 3.62-3.55 (m, 4H), 3.50 (t, J=9 Hz,1H), 3.37 (dt, J=9.4, 4.3 Hz, 1H), 3.31 (dd, J=9.8, 4.3 Hz, 1H),3.26-3.20 (m, 2H), 2.82 (d, J=4.2 Hz, 1H), 2.04, 2.03, 1.97 (s, 3Heach). ¹³C NMR δ 171.69, 170.67, 170.49, 166.99, 166.68, 166.53, 165.63,165.52, 164.92, 155.21, 150.12, 138.25, 137.82, 137.68, 137.59, 137.25,133.62, 133.55, 133.49, 129.86, 129.61, 129.51, 129.05, 128.76, 128.69,128.59, 128.39, 128.26, 128.11, 128.06, 127.96, 127.81, 127.78, 127.55,127.42, 127.18, 125.32, 118.28, 114.54, 100.85, 99.01, 98.79, 97.92,97.82, 97.49, 82.76, 79.71, 78:57, 78.36, 77.64, 75.43, 75.33, 75.19,74.75, 74.64, 74.24, 74.17, 73.41, 72.44, 72.36, 72.31, 71.27, 70.56,70.43, 70.26, 69.99, 68.06, 67.72, 65.57, 64.82, 64.72, 63.75, 63.31,63.09, 62.80, 62.08, 62.01, 55.69, 40.67, 40.44, 40.38, 20.79, 20.72.

Synthesis of 116

Compound 116 is prepared from compound 115 and 23 following generalprocedure E.

¹H NMR; (CDCl₃) δ 8.13-8.05 (m, 8H), 7.58-7.52 (m, 4H), 7.49-7.41 (m,10H), 7.37-7.11 (m, 43H), 7.01 (d, J=9.1 Hz, 2H), 6.83 (d, J=9.1 Hz,2H), 5.56 (s, 1H), 5.43-5.40 (m, 2H), 5.36-5.31 (m, 3H), 5.11 (t, J=4.1Hz, 1H), 5.05 (d, J=3.8 Hz, 1H), 4.96 (d, J=11.7 Hz, 1H), 4.91 (d,J=10.5 Hz, 1H), 4.86 (br s, 2H), 4.83-4.74 (m, 6H), 4.70-4.62 (m, 7H),4.59-4.55 (m, 3H), 4.48-4.45 (m, 1H), 4.30-4.12 (m, 16H), 4.06-3.56 (m,31H), 3.77 (s, 3H), 3.53-3.46 (m, 2H), 3.31-3.19 (m, 4H), 2.01, 2.00,1.97, 1.96 (s, 3H each). ¹³C NMR δ 170.49, 170.43, 166.82, 166.65,166.58, 166.53, 165.64, 165.44, 164.93, 155.23, 150.13, 138.24, 138.19,137.80, 137.60, 137.52, 137.24, 133.68, 133.56, 129.85, 129.62, 129.37,129.06, 128.78, 128.62, 128.57, 128.39, 128.36, 128.20, 128.12, 128.05,127.98, 127.79, 127.56, 127.43, 127.21, 125.32, 118.29, 114.55, 100.95,100.84, 98.81, 98.60, 98.00, 97.82, 97.51, 82.77, 80.13, 78.52, 78.36,78.06, 77.76, 77.61, 75.57, 75.43, 75.35, 75.29, 75.23, 75.18, 74.93,74.77, 74.63, 74.40, 74.17, 74.11, 73.49, 72.45, 72.37, 72.32, 70.35,70.26, 70.14, 70.01, 69.89, 68.08, 67.53, 65.59, 65.03, 64.82, 64.73,63.38, 63.32, 63.21, 62.40, 62.08, 61.91, 55.70, 40.59, 40.45, 40.38,20.77, 20.70.

Synthesis of 117

Compound 117 is prepared from compound 116 following general procedureF.

¹H NMR; (CDCl₃) δ 8.14-8.05 (m, 8H), 7.59-7.56 (m, 2H), 7.53-7.49 (m,2H), 7.47-7.41 (m, 10H), 7.37-7.12 (m, 43H), 7.01 (d, J=9.1 Hz, 2H),6.82 (d, J=9.1 Hz, 2H), 5.59 (s, 1H), 5.54 (d, J=4.0 Hz, 1H), 5.51 (d,J=3.9 Hz, 1H), 5.34-5.29 (m, 3H), 5.09 (t, J=2.4 Hz, 1H), 5.01 (s, 1H),4.98 (d, J=11.7 Hz, 1H), 4.86 (br s, 3H), 4.83-4.64 (m,11H), 4.58-4.53(m, 4H), 4.46 (d, J=2.8 Hz, 1H), 4.45 (d, J=2.8 Hz, 1H), 4.38 (t, J=6.8Hz, 1H), 4.29 (d, J=12.2 Hz, 1H), 4.22-3.62 (m, 29H), 3.77 (s, 3H),3.56-3.44 (m, 9H), 3.35-3.24 (m, 6H), 3.16-3.06 (m, 3H), 2.02, 2.00,1.96, 1.95 (s, 3H each). ¹³C NMR δ 170.57, 170.41, 165.71, 164.95,155.16, 150.33, 138.12, 137.77, 137.58, 137.47, 137.36, 137.31, 137.25,133.60, 133.44, 129.84, 129.63, 129.08, 128.74, 128.69, 128.56, 128.53,128.45, 128.35, 128.24, 128.06, 128.02, 127.87, 127.81, 127.76, 127.64,126.84, 126.79, 125.31, 118.22, 114.65, 101.27, 101.21, 98.58, 98.10,97.84, 97.69, 97.60, 97.36, 83.62, 80.25, 78.95, 78.47, 78.32, 78.13,78.01, 77.75, 75.54, 75.13, 75.04, 74.88, 74.80, 74.35, 74.27, 73.81,73.39, 73.11, 72.99, 72.74, 72.16, 72.06, 70.08, 69.93, 69.60, 68.80,68.33, 67.56, 63.49, 63.40, 63.22, 62.61, 62.39, 62.26, 62.10, 61.75,61.63, 61.30, 61.02, 55.66, 20.82, 20.73, 20.64.

Synthesis of 118

Compound 118 is prepared from compound 117 following general procedureG2.

¹H NMR; (CDCl₃) δ 8.12-8.05 (m, 8H), 7.60-7.42 (m, 12H), 7.38-7.09 (m,45H), 6.98 (d, J=9.1 Hz, 2H), 6.80 (d, J=9.1 Hz, 2H), 5.63 (s, 1H), 5.48(d, J=6.4 Hz, 1H), 5.45-5.37 (m, 4H), 5.29 (t, J=2.6 Hz, 1H), 5.15 (t,J=6.9 Hz, 1H), 5.03 (d, J=10.9 Hz, 1H), 4.95-4.91 (m, 3H), 4.88 (br s,2H), 4.83-4.55 (m, 15H), 4.44 (d, J=10.9 Hz, 1H), 4.31-3.42 (m, 31H),3.76, 3.52, 3.51, 3.50 (s, 3H each), 3.36-3.31 (m, 2H), 3.27 (dd,J=10.3, 3.8 Hz, 1H), 3.23 (dd, J=10.3, 3.6 Hz, 1H), 3.13 (dd, J=10.3,3.6 Hz, 1H), 2.97, 2.12, 2.03, 2.01, 2.01 (s, 3H each). ¹³C NMR δ170.87, 170.60, 170.43, 169.72, 169.16, 167.69, 167.49, 165.63, 165.08,164.69, 155.27, 150.54, 137.93, 137.56, 137.39, 137.18, 133.92, 133.63,129.94, 129.83, 129.73, 129.35, 129.03, 128.78, 128.54, 128.31, 128.17,128.06, 127.99, 127.91, 127.76, 127.59, 127.33, 118.10, 114.62, 101.18,98.68, 98.27, 97.69, 97.24, 82.80, 82.47, 80.22, 78.04, 77.82, 77.72,77.61, 75.95, 75.58, 75.31, 75.20, 75.01, 74.93, 74.82, 74.68, 74.53,73.65, 73.45, 72.67, 72.16, 71.56, 69.86, 69.54, 69.43, 69.30, 68.50,68.27, 63.41, 63.01, 62.88, 62.18, 61.54, 55.67, 52.69, 52.08, 51.96,51.86, 20.81.

Synthesis of 119

Compound 119 is prepared from compound 118 following general procedureH.

¹H NMR; (CDCl₃) δ 8.07-7.98 (m, 8H), 7.57-7.54 (m, 4H), 7.47-7.43 (m,8H), 7.35-7.02 (m, 45H), 6.96 (d, J=9.1 Hz, 2H), 6.78 (d, J=9.1 Hz, 2H),5.71-5.67 (m, 2H), 5.61-5.57 (m, 2H), 5.44-5.37 (m, 3H), 5,32 (m, 2H),5.19-5.16 (m, 2H), 5.02 (d, J=3.3 Hz, 1H), 4.96-4.77 (m, 10H), 4.69-4.47(m, 14H), 4.40-3.91 (m, 20H), 3.84-3.27 (m, 14H), 3.75, 3.52, 3.49,3.39, 3.29, 2.10, 2.01, 1.98, 1.94, 1.40, 1.39, 1.38, 1.30 (s, 3H each).¹³C NMR δ 171.11, 170.68, 170.62, 170.27, 170.08, 169.98, 169.26,168.92, 167.29, 167.23, 165.56, 165.37, 164.72, 155.38, 150.46, 138.70,138.57, 138.12, 137.70, 137.04, 136.85, 136.37, 133.93, 133.86, 129.78,129.73, 129.04, 128.98, 128.93, 128.88, 128.83, 128.71, 128.62, 128.57,128.52, 128.30, 128.24, 128.18, 128.09, 128.06, 128.00, 127.90, 127.77,127.67, 127.61, 127.32, 127.27, 118.11, 114.64, 101.35, 101.29, 99.60,98.87, 98.11, 97.85, 97.77, 97.70, 81.62, 81.40, 80.51, 77.98, 77.92,77.47, 75.45, 75.27, 75.18, 74.95, 74.85, 74.75, 74.67, 73.75, 73.59,73.52, 73.32, 73.22, 72.66, 71.94, 70.97, 70.71, 70.46, 69.84, 69.13,68.61, 66.97, 62.18, 61.60, 61.36, 55.65, 52.78, 52.52, 52.47, 52.17,52.09, 51.85, 51.78, 51.68, 22.74, 22.70, 22.61, 20.96, 20.82, 20.79,20.73.

Synthesis of 120

Compound 120 is prepared from compound 119 following general procedureI.

¹H NMR; (CDCl₃) δ 8.05-8.02 (m, 4H), 7.98 (d, J=7.3 Hz, 2H), 7.92 (d,J=7.3 Hz, 2H), 7.58-7.52 (m, 4H), 7.47-7.41 (m, 8H), 7.34-7.01 (m, 45H),6.93 (d, J=9.1 Hz, 2H), 6.75 (d, J=9.1 Hz, 2H), 5.72 (d, J=9.4 Hz, 1H),5.64 (d, J=8.9 Hz, 1H), 5.57-5.54 (m, 2H), 5.46-5.40 (m, 3H), 5.35-5.33(m, 2H), 5.20 (t, J=4.2 Hz, 1H), 5.13-5.11 (m, 2H), 4.99-4.48 (m, 24H),4.34 (d, J=12.2 Hz, 1H), 4.25-4.20 (m, 2H), 4.16-3.24 (m, 31H), 3.73,3.52, 3.44, 3.31, 3.27, 1.46, 1.43, 1.42, 1.34 (s, 3H each). ¹³C NMR; δ170.49, 170.16, 169.91, 169.06, 167.97, 167.87, 165.48, 164.79, 155.34,150.47, 138.91, 138.59, 138.30, 137.94, 137.07, 136.99, 136.52, 133.98,133.92, 133.84, 133.77, 129.74, 129.66, 129.54, 129.01, 128.86, 128.61,128.51, 128.28, 128.18, 128.05, 127.99, 127.85, 127.76, 127.68, 127.50,127.30, 118.04, 114.63, 100.81, 100.62, 99.07, 98.52, 98.42, 98.15,97.61, 97.24, 81.45, 81.34, 80.13, 77.74, 77.56, 76.49, 75.50, 75.24,74.98, 74.89, 74.67, 74.40, 73.76, 73.66, 73.33, 72.98, 72.85, 72.79,72.11, 71.89, 71.47, 70.71, 68.98, 68.72, 61.62, 60.50, 60.39, 59.98,55.64, 52.74, 52.65, 52.36, 52.25, 51.97, 51.77, 22.68, 22.65.

Synthesis of 121

Compound 121 is prepared from compound 120 following general procedureJ.

¹H NMR; (CD₃OD) δ 8.24-8.22 (m, 2H),8.18-8.16 (m, 2H), 8.11-8.09 (m,2H), 7.98-7.96 (m, 2H), 7.68-7.45 (m, 12H), 7.36-7.08 (m, 41H),6.98-6.96 (m, 4H), 6.92 (d, J=9.1 Hz, 2H), 6.83 (d, J=9.1 Hz, 2H), 5.57(d, J=4.5 Hz, 1H), 5.44 (d, J=3.0 Hz, 1H), 5.39-5.21 (m, 8H), 5.02-5.00(m, 2H), 4.96 (d, J=3.5 Hz, 1H), 4.90-4.52 (m, 24H), 4.47-4.43 (m, 2H),4.37-4.08 (m, 15H), 4.03-3.93 (m, 6H), 3.76-3.65 (m, 3H), 3.75 (s, 3H),3.62-3.55 (m, 4H), 3.57 (s, 3H), 3.46-3.41 (m, 2H), 3.24, 2.98, 1.86,1.84, 1.59, 1.53 (s, 3H each). ¹³C NMR; δ 173.58, 173.35, 171.09,170.61, 170.40, 170.26, 167.34, 167.12, 166.58, 157.06, 152.01, 140.26,140.16, 140.07, 139.92, 139.87, 139.01, 138.71, 138.47, 135.13, 134.99,134.85, 134.66, 131.24, 131.16, 130.93, 130.86, 130.66, 130.52, 130.22,129.97, 129.52, 129.37, 129.32, 129.25, 129.21, 129.16, 129.07, 128.99,128.85, 128.68, 128.61, 128.42, 128.18, 119.64, 115.74, 101.96, 101.68,99.95, 98.97, 98.71, 97.33, 84.05, 83.94, 81.71, 79.93, 79.41, 79.12,78.98, 78.76, 78.17, 76.52, 76.23, 76.10, 75.85, 75.69, 75.41, 75.07,75.01, 74.48, 74.07, 73.82, 72.54, 71.77, 71.59, 71.48, 70.95, 70.09,66.85, 66.08, 65.74, 56.19, 54.09, 53.78, 53.49, 53.36, 53.10, 53.02,52.58, 22.94, 22.85, 22.65.

Synthesis of 122

Compound 122 is prepared from compound 121 following general procedureK.

¹H NMR; (CD₃OD) δ 7.43-7.19 (m, 45H), 7.07 (d, J=9.1 Hz, 2H), 6.84 (d,J=9.1 Hz, 2H), 5.47 (d, J=1.2 Hz, 1H), 5.41 (d, J=3.8 Hz, 1H), 5.39 (d,J=3.8 Hz, 1H), 5.22 (d, J=2.5 Hz, 1H), 5.09-4.54 (m, 22H), 4.44 (d,J=11.8 Hz, 1H), 4.37-3.68 (m, 35H), 3.74 (s, 3H), 3.63-3.52 (m, 4H),1.86, 1.78, 1.77, 1.70 (s, 3H each). ¹³C NMR; δ 177.80, 176.22, 176.04,175.71, 175.63, 173.33, 173.16, 173.08, 156.51, 152.45, 140.40, 140.28,140.15, 139.88, 139.55, 139.37, 129.48, 129.43, 129.37, 129.31, 129.25,129.05, 128.96, 128.86, 128.79, 128.56, 128.45, 119.34, 115.66, 104.07,103.96, 102.07, 101.71, 98.54, 98.46, 97.09, 96.08, 85.87, 81.97, 81.07,80.82, 80.48, 79.38, 78.42, 77.64, 77.51, 76.65, 76.30, 75.94, 75.58,75.13, 75.00, 74.70, 74.32, 73.12, 72.93, 72.32, 71.32, 71.18, 71.09,70.55, 70.11, 68.49, 67.49, 67.07, 56.13, 54.45, 53.64, 53.59, 22.97,22.52.

Synthesis of 123

Compound 123 is prepared from compound 122 following general procedureL.

¹H NMR; (D₂O) δ 6.99 (d, J=8.3 Hz, 2H), 6.83 (d, J=8.3 Hz, 2H), 5.30 (s,1H), 5.26 (s, 1H), 5.22 (s, 1H), 5.02-4.99 (m, 2H), 4.82 (s, 1H),4.61-4.54 (br s, HOD and 2H), 4.43-4.41 (m, 2H), 4.30-4.28 (m, 2H),4.20-4.17 (m, 2H), 4.08-4.00 (m, 5H), 3.95-3.72 (m, 13H), 3.67-3.54 (m,16H), 3.41 (t, J=9.4 Hz, 1H), 3.20-3.17 (m, 2H), 1.89, 1.85 (s, 6Heach). ¹³C NMR δ 175.07, 174.76, 174.53, 174.49, 174.43, 174.38, 154.82,150.34, 119.38, 115.19, 102.04, 101.96, 101.90, 100.72, 97.11, 97.06,94.49, 94.35, 77.39, 77.16, 76.90, 76.63, 76.57, 76.28, 76.19, 74.34,73.84, 73.56, 70.66, 70.10, 69.57, 69.40, 69.28, 69.23, 69.16, 68.96,68.88, 68.08, 66.41, 66.23, 65.92, 55.93, 53.76, 53.60, 53.05, 22.06,22.02.

Synthesis of 124

Compound 124 is prepared from compounds 24 and 27 following generalprocedure E.

¹H NMR; (CDCl₃) δ 8.11-8.05 (m, 4H), 7.76 (d, J=7.6 Hz, 2H), 7.60-7.54(m, 3H), 7.50-7.13 (m, 27H), 7.09-7.07 (m, 2H), 6.89 (d, J=9.1 Hz, 2H),6.76 (d, J=9.1 Hz, 2H), 5.55-5.52 (m, 2H), 5.17 (t, J=3.7 Hz, 1H), 5.14(d, J=3.4 Hz, 1H), 5.08 (d, J=7.1 Hz, 1H), 4.97 (d, J=10.4 Hz, 1H), 4.85(d, J=11.3 Hz, 1H), 4.81-4.74 (m, 5H), 4.70 (d, J=10.4 Hz, 1H), 4.61(dd, J=11.5, 2.6 Hz, 1H), 4.52-4.48 (m, 2H), 4.44-4.41 (m, 1H),4.36-4.28 (m, 3H), 4.26-4.21 (m, 4H), 4.18 (t, J=6.8 Hz, 1H), 4.12-3.94(m, 10H), 3.90-3.80 (m, 4H), 3.74 (s, 3H), 3.72-3.68 (m, 2H), 3.34-3.31(m, 2H), 2.06, 2.00 (s, 3H each). ¹³C NMR; δ 170.60, 170.50, 166.87,166.83, 165.45, 165.11, 155.72, 154.19, 150.99, 143.20, 143.05, 141.34,137.85, 137.34, 137.21, 137.06, 133.59, 133.49, 129.83, 129.50, 129.46,129.06, 128.76, 128.61, 128.46, 128.42, 128.31, 128.25, 128.18, 128.01,127.89, 127.81, 127.67, 127.27, 125.32, 125.04, 124.85, 120.14, 118.77,114.57, 100.13, 98.86, 97.99, 97.79, 82.77, 78.64, 77.89, 75.41, 75.28,75.18, 75.03, 74.56, 74.22, 74.13, 73.65, 73.43, 72.54, 70.32, 69.97,68.81, 67.30, 64.65, 63.84, 63.36, 63.11, 62.25, 61.96, 55.66, 46.76,40.66, 40.55, 20.79, 20.64.

Synthesis of 125

Compound 125 is prepared from compound 124 following general procedureD.

¹H NMR; (CDCl₃) δ 8.11-8.09 (m, 2H), 8.07-8.05 (m, 2H), 7.57 (t, J=7.4Hz, 1H), 7.52 (t, J=7.4 Hz, 1H), 7.46-7.43 (m, 4H), 7.37-7.19 (m, 20H),6.88 (d, J=9.1 Hz, 2H), 6.76 (d, J=9.1 Hz, 2H), 5.55-5.52 (m, 2H), 5.18(t, J=4.2 Hz, 1H), 5.12 (d, J=3.9 Hz, 1H), 5.07 (d, J=7.1 Hz, 1H), 4.97(d, J=10.3 Hz, 1H), 4.84 (d, J=11.3 Hz, 1H), 4.80-4.75 (m, 4H), 4.69 (d,J=10.3 Hz, 1H), 4.61-4.47 (m, 4H), 4.43 (d, J=10.8 Hz, 1H), 4.39-4.34(m, 2H), 4.29 (dd, J=11.8, 5.8 Hz, 1H), 4.20 (d, J=11.6 Hz, 1H),4.16-4.05 (m, 4H), 4.00 (t, J=8.7 Hz, 1H), 3.94-3.93 (m, 4H), 3.88-3.79(m, 4H), 3.75-3.71 (m, 2H), 3.74 (s, 3H), 3.58 (dd, J=10.0, 8.8 Hz, 1H),3.40-3.36 (m, 1H), 3.32 (dd, J=9.7, 4.0 Hz, 1H), 3.22 (dd, J=10.1, 3.7Hz, 1H), 2.82 (d, J=4.2 Hz, 1H), 2.06, 2.04 (s, 3H each). ¹³C NMR; δ171.69, 170.74, 167.01, 166.75, 165.49, 165.08, 155.69, 150.98, 137.87,137.68, 137.34, 137.26, 133.53, 133.47, 129.83, 129.49, 129.44, 128.70,128.59, 128.41, 128.33, 128.26, 128.10, 127.79, 127.66, 118.75, 114.55,100.10, 99.00, 97,93, 97.78, 82.74, 79.68, 78.51, 75.61, 75.30, 75.20,74.73, 74.56, 74.21, 73.62, 73.50, 72.52, 71.26, 70.62, 70.56, 70.29,67.94, 64.60, 63.69, 63.27, 63.06, 62.81, 62.20, 55.65, 40.67, 40.52,20.78, 20.72.

Synthesis of 126

Compound 126 is prepared from compounds 125 and 22 following generalprocedure E.

¹H NMR; (CDCl₃) δ 8.10-8.05 (m, 6H), 7.76-7.73 (m, 2H), 7.59-7.53 (m,5H), 7.47-7.42 (m, 6H), 7.39-7.36 (m, 2H), 7.31-7.13 (m, 32H), 6.88 (d,J=9.1 Hz, 2H), 6.76 (d, J=9.1 Hz, 2H), 5.54-5.51 (m, 2H), 5.47 (d, J=3.8Hz, 1H), 5.36 (t, J=8.1 Hz, 1H), 5.14 (t, J=4.4 Hz, 1H), 5.07-5.06 (m,2H), 4.91 (d, J=10.5 Hz, 1H), 4.88-4.84 (m, 2H), 4.80-4.62 (m, 10H),4.57 (dd, J=11.7, 2.5 Hz, 1H), 4.47 (dd, J=10.4, 6.7 Hz, 1H), 4.33-4.13(m, 11H), 4.08-3.75 (m, 23H), 3.73 (s, 3H), 3.67-3.59 (m, 4H), 3.35 (dd,J=10.3, 3.9 Hz, 1H), 3.29 (dd, J=9.6, 4.0 Hz, 1H), 3.23 (dd, J=9.7, 3.8Hz, 1H), 2.03, 2.02, 1.97 (s, 3H each). ¹³C NMR; δ 170.58, 170.44,166.87, 166.74, 166.62, 165.43, 165.08, 164.93, 155.70, 154.12, 150.99,143.25, 143.01, 141.34, 138.23, 137.86, 137.36, 137.25, 137.14, 137.09,133.74, 133.61, 133.47, 129.83, 129.52, 129.32, 129.06, 128.82, 128.75,128.60, 128.41, 128.32, 128.21, 127.98, 127.93, 127.80, 127.68, 127.57,127.24, 125.33, 125.11, 124.91, 120.13, 118.77, 114.56, 100.94, 100.11,98.62, 97.82, 82.74, 82.68, 78.46, 78.06, 77.76, 77.48, 75.67, 75.32,75.20, 74.97, 74.77, 74.58, 74.22, 74.08, 73.58, 72.54, 72.32, 70.40,70.31, 69.88, 68.77, 67.71, 64.96, 64.59, 63.36, 63.26, 63.17, 62.61,62.13, 61.94, 61.81, 55.65, 46.71, 40.60, 40.53, 40.43, 20.77, 20.70.

Synthesis of 127

Compound 127 is prepared from compound 126 following general procedureD.

¹H NMR; (CDCl₃) δ 8.10-8.04 (m, 6H), 7.58-7.53 (m, 3H), 7.47-7.41 (m,6H), 7.40-7.35 (m, 4H), 7.32-7.13 (m, 26H), 6.88 (d, J=9.1 Hz, 2H), 6.76(d, J=9.1 Hz, 2H), 5.54-5.51 (m, 2H), 5.44 (d, J=3.9 Hz, 1H), 5.35 (t,J=8.2 Hz, 1H), 5.14 (t, J=4.4 Hz, 1H), 5.07-5.05 (m, 2H), 4.92-4.83 (m,4H), 4.80-4.76 (m, 4H), 4.73-4.64 (m, 5H), 4.57 (dd, J=11.8, 2.6 Hz,1H), 4.51 (dd, J=12.5, 3.6 Hz, 1H), 4.33-4.11 (m, 9H), 4.08-3.92 (m,9H), 3.87-3.72 (m, 10H), 3.73 (s, 3H), 3.66-3.58 (m, 6H), 3.41 (dt,J=9.5, 3.9 Hz, 1H), 3.29 (dd, J=9.6, 3.9 Hz, 1H), 3.24 (t, J=4.5 Hz,1H), 3.22 (t, J=4.1 Hz, 1H), 2.92 (d, J=4.0 Hz, 1H), 2.07, 2.03, 1.96(s, 3H each). ¹³C NMR; δ 171.88, 170.57, 170.47, 166.90, 166.73, 166.61,165.42, 165.08, 164.95, 155.70, 150.99, 138.27, 137.85, 137.78, 137.35,137.25, 137.21, 133.71, 133.60, 133.46, 129.82, 129.52, 129.32, 129.05,128.80, 128.74, 128.67, 128.59, 128.39, 128.31, 128.24, 128.20, 128.04,127.96, 127.79, 127.72, 127.67, 127.60, 127.54, 127.16, 125.32, 118.77,114.56, 100.92, 100.11, 98.61, 98.22, 97.83, 97.78, 82.81, 82.74, 79.16,78.45, 78.05, 77.78, 75.66, 75.42, 75.25, 75.02, 74.96, 74.72, 74.57,74.21, 74.15, 73.62, 73.57, 72.54, 72.44, 71.36, 70.62, 70.30, 69.88,67.71, 64.92, 64.58, 63.34, 63.25, 63.15, 62.72, 62.66, 62.13, 61.95,55.65, 40.59, 40.52, 40.43, 20.78, 20.70.

Synthesis of 128

Compound 128 is prepared from compound 127 and 25 following generalprocedure E.

¹H NMR; (CDCl₃) δ 8.09-8.04 (m, 8H), 7.58-7.54 (m, 3H), 7.47-7.43 (m,7H), 7.39-7.12 (m, 47H), 6.88 (d, J=9.1 Hz, 2H), 6.76 (d, J=9.1 Hz, 2H),5.54-5.50 (m, 2H), 5.41 (d, J=3.9 Hz, 1H), 5.33 (t, J=8.2 Hz, 1H),5.14-5.11 (m, 3H), 5.07-5.05 (m, 2H), 4.97 (d, J=11.3 Hz, 1H), 4.91 (d,J=10.4 Hz, 1H), 4.84-4.81 (m, 2H), 4.79-4.62 (m, 10H), 4.57 (dd, J=11.7,2.5 Hz, 1H), 4.53-4.47 (m, 3H), 4.38 (m, 1H), 4.33-3.91 (m, 22H),3.86-3.59 (m, 15H), 3.73 (s, 3H), 3.42 (t, J=9.5 Hz, 1H), 3.31-3.21 (m,4H), 2.03, 2.02, 1.98, 1.96 (s, 3H each). ¹³C NMR; δ 170.57, 170.51,170.41, 166.86, 166.70, 166.61, 165.48, 165.40, 165.07, 164.92, 155.69,150.98, 138.22, 137.84, 137.77, 137.45, 137.35, 137.24, 133.60, 133.45,129.84, 129.51, 129.30, 129.05, 128.78, 128.74, 128.70, 128.62, 128.48,128.39, 128.29, 128.24, 128.19, 128.11, 128.06, 127.97, 127.84, 127.79,127.72, 127.67, 127.53, 127.26, 125.32, 118.77, 114.54, 100.90, 100.10,98.80, 98.61, 97.99, 97.77, 82.78, 82.73, 80.41, 78.64, 78.44, 77.99,77.72, 77.62, 75.69, 75.34, 75.22, 75.16, 74.92, 74.74, 74.67, 74.58,74.21, 74.15, 73.60, 73.43, 72.53, 72.36, 70.31, 70.11, 69.88, 67.76,67.52, 64.76, 64.57, 63.80, 63.66, 63.32, 63.23, 63.12, 62.60, 62.10,61.98, 61.88, 55.64, 40.67, 40.59, 40.51, 40.41, 20.76, 20.72.

Synthesis of 129

Compound 129 is prepared from compound 128 following general procedureF.

¹H NMR; (CDCl₃) δ 8.11-8.04 (m, 8H), 7.59-7.50 (m, 3H), 7.47-7.12 (m,54H), 6.89 (d, J=9.1 Hz, 2H), 6.76 (d, J=9.1 Hz, 2H), 5.63 (d, J=3.9 Hz,1H), 5.56-5.53 (m, 2H), 5.32 (dd, J=8.8, 8.3 Hz, 1H), 5.14-5.10 (m, 3H),5.05-5.04 (m, 2H), 4.88-4.84 (m, 2H), 4.82-4.62 (m, 14H), 4.51-4.46 (m,3H), 4.33-4.03 (m, 16H), 3.97-3.65 (m, 18H), 3.73 (s, 3H), 3.58-3.50 (m,6H), 3.41-3.37 (m, 2H), 3.33-3.26 (m, 6H), 3.19-3.11 (m, 2H), 2.03 (s,6H), 1.99, 1.97 (s, 3H each). ¹³C NMR; δ 170.57, 170.52, 170.48, 170.42,165.76, 165.71, 165.09, 164.95, 155.64, 151.12, 138.12, 137.88, 137.68,137.59, 137.53, 137.48, 137.38, 137.35, 137.23, 133.63, 133.48, 133.39,133.32, 129.83, 129.60, 129.06, 128.76, 128.68, 128.62, 128.56, 128.51,128.41, 128.25, 128.13, 128.08, 127.96, 127.92, 127.84, 127.79, 127.75,127.66, 126.89, 125.32, 118.52, 114.65, 101.21, 100.52, 98.21, 97.90,97.41, 97.35, 83.64, 83.33, 80.64, 78.98, 78.74, 78.30, 77.96, 77.80,75.25, 75.17, 75.10, 75.04, 74.89, 74.48, 74.43, 74.37, 74.32, 74.07,73.95, 73.78, 73.44, 73.32, 73.16, 72.87, 72.51, 70.19, 70.07, 70.03,69.65, 69.18, 67.97, 67.86, 63.83, 63.52, 63.41, 62.80, 62.62, 62.29,62.14, 61.94, 61.71, 61.27, 61.04, 55.64, 20.83, 20.80, 20.75.

Synthesis of 130

Compound 130 is prepared from compound 129 following general procedureG2.

¹H NMR; (CDCl₃) δ 8.12-8.09 (m, 4H), 8.06-8.01 (m, 4H), 7.57-7.53 (m,3H), 7.49-7.13 (m, 52H), 7.09-7.07 (m, 2H), 6.84 (d, J=9.1 Hz, 2H), 6.73(d, J=9.1 Hz, 2H), 5.51-5.47 (m, 4H), 5.44 (d, J=3.8 Hz, 1H), 5.38 (t,J=8.9 Hz, 1H), 5.17-5.15 (m, 2H), 5.06 (d, J=6.8 Hz, 1H), 5.01 (d,J=10.3 Hz, 1H), 4.98-4.96 (m, 2H), 4.93-4.90 (m, 2H), 4.80-4.62 (m,13H), 4.56 (d, J=10.9 Hz, 1H), 4.48-4.38 (m, 3H), 4.34-4.29 (m, 4H),4.26-4.01 (m, 12H), 3.96-3.63 (m, 11H), 3.72, 3.64 (s, 3H each),3.55-3.48 (m, 2H), 3.49 (s, 3H), 3.44-3.41 (m, 2H), 3.31-3.19 (m, 4H),3.21, 3.13, 2.12, 2.11, 2.00, 1.96 (s, 3H each). ¹³C NMR; δ 170.83,170.75, 170.47, 170.39, 169.70, 169.53, 168.10, 167.58, 165.23, 165.15,164.99, 164.65, 155.68, 150.94, 137.97, 137.88, 137.84, 137.66, 137.54,137.42, 137.30, 137.10, 133.93, 133.68, 133.51, 133.43, 129.97, 129.93,129.79, 129.72, 129.45, 129.21, 129.05, 128.86, 128.80, 128.52, 128.48,128.40, 128.33, 128.30, 128.16, 128.08, 127.96, 127.91, 127.88, 127.80,127.58, 125.32, 118.73, 114.48, 101.18, 100.72, 99.17, 98.67, 98.24,97.75, 97.39, 97.35, 82.71, 82.18, 80.00, 78.30, 77.93, 77.68, 77.60,77.51, 76.05, 75.94, 75.54, 75.39, 75.19, 75.12, 75.02, 74.80, 74.75,74.62, 74.52, 74.33, 74.21, 74.08, 73.80, 73.68, 72.06, 71.47, 70.75,70.41, 70.11, 69.40, 63.51, 63.11, 62.90, 62.83, 62.29, 61.67, 61.53,55.61, 52.19, 52.15, 52.08, 51.85, 20.81.

Synthesis of 131

Compound 131 is prepared from compound 130 following general procedureH.

¹H NMR; (CDCl₃) δ 8.09-8.06 (m, 2H), 8.04-8.00 (m, 6H), 7.59-7.51 (m,4H), 7.48-7.38 (m, 8H), 7.35-7.06 (m, 45H), 6.84 (d, J=9.1 Hz, 2H), 6.73(d, J=9.1 Hz, 2H), 5.75 (d, J=9.5 Hz, 1H), 5.68-5.60 (m, 3H), 5.52 (dd,J=8.5, 6.7 Hz, 1H), 5.42-5.37 (m, 2H), 5.33 (d, J=5.6 Hz, 1H), 5.19-5.17(m, 2H), 5.06-5.05 (m, 2H), 5.01 (d, J=3.3 Hz, 1H), 4.94-4.75 (m, 8H),4.69-4.47 (m, 13H), 4.42-3.92 (m, 23H), 3.86-3.46 (m, 11H), 3.71, 3.62,3.53 (s, 3H each), 3.41-3.32 (m, 1H), 3.40, 3.34 (s, 3H each), 2.11,2.10, 1.99, 1.93, 1.50, 1.39, 1.38, 1.36 (s, 3H each). ¹³C NMR; δ171.13, 171.04, 170.66, 170.57, 170.26, 170.17, 170.0, 169.97, 169.28,169.20, 167.69, 167.28, 165.55, 165.42, 164.99, 164.70, 155.75, 150.86,138.74, 138.59, 138.39, 138.05, 137.81, 136.89, 136.52, 136.34, 133.94,133.84, 133.58, 129.75, 129.27, 129.04, 128.98, 128.93, 128.75, 128.62,128.59, 128.47, 128.27, 128.18, 128.05, 127.79, 127.61, 127.56, 127.43,127.35, 127.32, 125.31, 118.63, 114.52, 101.36, 100.90, 99.21, 99.05,98.00, 97.91, 97.87, 97.73, 81.58, 80.95, 80.52, 78.08, 77.91, 75.58,75.29, 74.97, 74.92, 74.84, 74.76, 74.50, 73.86, 73.77, 73.62, 73.49,73.34, 72.87, 72.01, 71.10, 71.03, 70.61, 70.51, 70.37, 70.12, 69.82,62.44, 61.69, 61.52, 55.61, 52.68, 52.57, 52.41, 52.09, 51.81, 22.95,22.76, 22.58, 20.98, 20.76.

Synthesis of 132

Compound 132 is prepared from compound 131 following general procedureI.

¹H NMR; (CDCl₃) δ 8.05-7.94 (m, 8H), 7.59-7.54 (m, 3H), 7.51-7.10 (m,54H), 6.84 (d, J=9.1 Hz, 2H), 6.73 (d, J=9.1 Hz, 2H), 5.65 (d, J=9.3 Hz,1H), 5.61 (d, J=9.3 Hz, 1H), 5.58-5.51 (m, 3H), 5.45 (d, J=4.3 Hz, 1H),5.41 (t, J=8.2 Hz, 1H), 5.35 (d, J=5.2 Hz, 1H), 5.23-5.20 (m, 2H), 5.11(d, J=3.4 Hz, 1H), 5.08-5.05 (m, 2H), 4.93-4.87 (m, 5H), 4.81-4.77 (m,3H), 4.74-4.69 (m, 2H), 4.67-4.61 (m, 6H), 4.57-4.49 (m, 5H), 4.35-4.20(m, 6H), 4.13-3.89 (m, 12H), 3.85 (t, J=8.2 Hz, 1H), 3.79 (d, J=10.2 Hz,1H), 3.71 (s, 3H), 3.70-3.29 (m, 16H), 3.62, 3.56, 3.37, 3.27 (s, 3Heach), 1.55, 1.45, 1.44, 1.41 (s, 3H each). ¹³C NMR; δ 170.45, 170.34,169.94, 169.30, 168.98, 167.94, 165.56, 165.41, 164.99, 164.76, 155.75,150.86, 138.98, 138.53, 138.46, 138.21, 138.09, 136.99, 136.52, 133.86,133.58, 129.75, 129.64, 129.55, 129.26, 129.01, 128.90, 128.58, 128.51,128.45, 128.25, 128.15, 128.03, 127.99, 127.92, 127.85, 127.76, 127.61,127.42, 127.29, 118.61, 114.52, 100.87, 100.63, 98.87, 98.49, 97.81,97.67, 97.47, 97.23, 81.38, 81.06, 79.84, 77.83, 76.59, 76.46, 75.37,74.96, 74.75, 74.62, 74.49, 74.41, 74.03, 73.78, 73.34, 73.15, 73.02,72.86, 72.77, 72.54, 71.91, 71.34, 70.91, 70.60, 70.02, 66.54, 66.36,61.61, 60.83, 60.63, 60.39, 60.00, 55.61, 52.70, 52.58, 52.45, 52.22,52.05, 51.78, 22.92, 22.70, 22.61.

Synthesis of 133

Compound 133 is prepared from compound 132 following general procedureJ.

¹H NMR; (CD₃OD) δ 8.28 (d, J=7.5 Hz, 2H), 8.11-8.05 (m, 6H), 7.65 (t,J=7.3 Hz, 1H), 7.58-7.07 (m, 52H), 7.02-7.00 (m, 2H), 6.93-6.91 (m, 2H),6.87 (d, J=9.1 Hz, 2H), 6.77 (d, J=9.1 Hz, 2H), 5.58-5.52 (m, 3H),5.43-5.38 (m, 3H), 5.27-5.21 (m, 4H), 5.08 (d, J=3.0 Hz, 1H), 5.00-4.97(m, 2H), 4.93 (d, J=2.4 Hz, 1H), 4.82-4.10 (m, 38H), 4.00-3.95 (m, 3H),3.87-3.84 (m, 2H), 3.69-3.30 (m, 21H), 2.90 (s, 3H), 1.86, 1.82, 1.66,1.52 (s, 3H each). ¹³C NMR; δ 173.60, 173.43, 173.34, 173.25, 171.20,170.46, 170.34, 167.38, 167.28, 166.95, 166.57, 164.90, 157.13, 152.29,140.19, 140.02, 139.97, 139.79, 138.92, 138.64, 138.54, 138.38, 135.15,134.81, 134.64, 134.53, 131.24, 130.96, 130.87, 130.81, 130.68, 130.22,129.99, 129.80, 129.62, 129.54, 129.43, 129.33, 129.21, 129.10, 128.93,128.81, 128.52, 128.42, 128.05, 119.10, 115.70, 101.82, 101.19, 99.17,99.11, 99.00, 98.57, 97.03, 84.18, 83.38, 81.40, 79.97, 79.56, 79.17,78.60, 76.27, 76.05, 75.59, 75.39, 75.27, 75.20, 74.95, 74.62, 74.36,74.19, 73.37, 72.39, 72.16, 71.72, 71.58, 71.50, 71.24, 70.74, 70.39,67.24, 66.20, 66.11, 65.87, 56.22, 54.40, 53.91, 53.60, 53.48, 53.24,53.16, 53.08, 52.44, 49.94, 22.96, 22.91, 22.79.

Synthesis of 134

Compound 134 is prepared from compound 133 following general procedureK.

¹H NMR; (CD₃OD) δ 7.43-7.11 (m, 45H), 7.04 (d, J=9.1 Hz, 2H), 6.84 (d,J=9.1 Hz, 2H), 5.41-5.39 (m, 2H), 5.25-5.23 (m, 2H), 5.09 (d, J=5.2 Hz,1H), 5.07 (d, J=5.3 Hz, 1H), 4.98 (d, J=12.3 Hz, 1H), 4.91-4.69 (m,11H), 4.66-4.54 (m, 8H), 4.45 (d, J=11.7 Hz, 1H), 4.39 (d, J=11.6 Hz,1H), 4.36-4.24 (m, 5H), 4.18-3.61 (m, 32H), 3.75 (s, 3H), 3.51 (t, J=8.3Hz, 1H), 1.82, 1.78, 1.77, 1.68 (s, 3H each). ¹³C NMR; δ 175.64, 175.38,174.72, 173.31, 173.17, 172.98, 156.89, 153.22, 140.30, 140.21, 140.10,139.89, 139.86, 139.75, 139.71, 139.34, 139.24, 129.75, 129.64, 129.59,129.52, 129.40, 129.35, 129.26, 129.02, 128.88, 128.76, 128.69, 128.64,128.56, 128.48, 128.35, 128.16, 127.94, 119.55, 115.55, 103.92, 103.86,102.02, 101.68, 98.78, 98.59, 98.04, 97.25, 86.18, 85.89, 82.13, 80.94,80.68, 80.42, 79.09, 78.25, 77.72, 76.58, 76.23, 76.09, 75.81, 75.43,75.22, 75.08, 74.55, 74.15, 73.13, 71.62, 71.38, 70.33, 69.77, 69.45,68.96, 67.50, 67.20, 67.03, 56.14, 54.43, 54.24, 53.62, 49.91, 49.70,22.97.

Synthesis of 135

Compound 135 is prepared from compound 134 following general procedureL.

¹H NMR; (D₂O) δ 7.10 (d, J=7.5 Hz, 2H), 6.97 (d, J=7.5 Hz, 2H),5.40-5.38 (m, 2H), 5.16 (s, 2H), 4.99-4.98 (m, 3H), 4.77 (br s, 2H),4.57 (d, J=7.6 Hz, 1H), 4.44 (d, J=10.8 Hz, 1H), 4.35-4.33 (m, 3H),4.23-4.18 (m, 4H), 4.08-4.06 (m, 3H), 4.03-4.01 (m, 2H), 3.97-3.89 (m,8H), 3.85-3.69 (m, 14H), 3.81 (s, 3H), 3.59-3.54 (m, 2H), 3.34 (t, J=8.2Hz, 1H), 2.05 (s, 6H), 2.02, 2.01 (s, 3H each). ¹³C NMR; δ 175.04,174.71, 174.53, 174.45, 154.87, 151.03, 118.39, 115.16, 102.02, 101.96,101.86, 101.30, 97.20, 97.14, 94.53, 94.34, 77.30, 77.11, 76.81, 76.61,76.43, 76.21, 74.22, 73.59, 73.38, 71.14, 70.23, 69.61, 69.39, 69.25,68.98, 68.80, 66.54, 66.24, 65.93, 55.94, 53.78, 53.49, 53.05, 22.03.

Example 3 X-Ray Crystal Structure Analysis of Compounds 13, 14, 15, 16and 27

Compound 13 is synthesised as described in Example 2 (GPA), andcrystallised from hot toluene by addition of petroleum ether. X-Rayquality crystals are obtained by vapor diffusion of petroleum ether intoa solution of 13 in toluene.

Compound 14 is synthesised as described in Example 2 (GPA), andcrystallised from toluene by addition of petroleum ether. X-Ray qualitycrystals are obtained by vapor diffusion of petroleum ether into asolution of 14 in toluene.

Compound 15 is synthesised as described in Example 2 (GPA), andcrystallised from toluene by addition of petroleum ether. X-Ray qualitycrystals are obtained by vapor diffusion of petroleum ether into asolution of 15 in toluene.

Compound 16 is synthesised as described in Example 2 (GPA), andcrystallised from ethyl acetate by addition of petroleum ether.

Compound 27 is synthesised as described in Example 2 (GPD), andcrystallises directly after elution from the chromatography column.X-Ray quality crystals are obtained by vapor diffusion of petroleumether into a solution of 27 in toluene.

Crystals of compound 13 contain two enantiomerically identical moleculeswhich are aligned along the a axis and separated by almost exactly byhalf a cell (shown in FIG. 1).

Data are collected on a Bruker APEXII diffractometer. Computing detailsare as follows: data collection: CrystalClear (Rigaku, 2005); cellrefinement: FSProcess (Rigaku, 1998); data reduction: FSProcess (Rigaku,1998); program used to solve structure: SHELXS97 (Sheldrick, 2008);program used to refine structure: SHELXL97 (Sheldrick, 1997); moleculargraphics: ORTEP in WinGX (Farrugia, 1999).

TABLE 1 Crystal Data for Compound 13 Empirical formula C59 H56 Cl N3 O16Formula weight 1098.52 Temperature 123(2) K Wavelength 1.54178 A Crystalsystem, space group Monoclinic, P 21 Unit cell dimensions a = 10.454(2)A alpha = 90 deg. b = 35.610(7) A beta = 95.61(3) deg. c = 14.408(3) Agamma = 90 deg. Volume 5338.0(19) A{circumflex over ( )}3 Z, Calculateddensity 4, 1.367 Mg/m{circumflex over ( )}3 Absorption coefficient 1.271mm{circumflex over ( )}−1 F(000) 2304 Crystal size 0.85 × 0.08 × ?0.04mm Theta range for data collection 6.54 to 55.00 deg. Limiting indices−10 <= h <= 8, −37 <= k <= 37, −15 <= l <= 15 Reflectionscollected/unique 35705/12625 [R(int) = 0.0554] Completeness to theta =55.00 97.7% Absorption correction Semi-empirical from equivalentsRefinement method Full-matrix least-squares on F{circumflex over ( )}2Data/restraints/parameters 12625/3/1426 Goodness-of-fit on F{circumflexover ( )}2 0.997 Final R indices [I > 2sigma(I)] R1 = 0.0575, wR2 =0.1332 R indices (all data) R1 = 0.0840, wR2 = 0.1554 Absolute structureparameter 0.033(19) Largest diff. peak and hole 0.318 and −0.301e.A{circumflex over ( )}−3

TABLE 2 Crystal Data for Compound 14 Empirical formula C51 H52 Cl N3 O14Formula weight 966.41 Temperature 164(2) K Wavelength 1.54178 Å Crystalsystem, space group Monoclinic, P 2₁ Unit cell dimensions a = 9.2713(7)Å, alpha = 90 deg. b = 17.4067(11) Å, beta = 97.449(7) deg. c =15.0036(11) Å, gamma = 90 deg. Volume 2400.9(3) Å³ Z, Calculated density2, 1.337 Mg/m³ Absorption coefficient 1.302 mm⁻¹ F(000) 1016 Crystalsize 0.85 × 0.45 × 0.14 mm Theta range for data collection 7.01 to 60.01deg. Limiting indices −10 <= h <= 10, −19 <= k <= 14, −16 <= l <= 16Reflections collected/unique 15021/5678 [R(int) = 0.0556] Completenessto theta = 60.01 99.2% Absorption correction Semi-empirical fromequivalents Max. and min. transmission 1.0, 0.521 Refinement methodFull-matrix least-squares on F² Data/restraints/parameters 5678/3/558Goodness-of-fit on F² 1.093 Final R indices [I > 2sigma(I)] R1 = 0.0596,wR2 = 0.1600 R indices (all data) R1 = 0.0695, wR2 = 0.1714 Absolutestructure parameter 0.02(3) (Flack, 1983) Extinction coefficient0.0023(4) Largest diff. peak and hole 0.311 and −0.316 e.A⁻³

TABLE 3 Crystal Data for Compound 15 Empirical formula C52 H55 N3 O15Formula weight 961.99 Temperature 118(2) K Wavelength 0.71073 Å Crystalsystem, space group Monoclinic, C2 Unit cell dimensions a = 38.3346(13)Å alpha = 90 deg. b = 8.0744(3) Å beta = 91.222(2) deg. c = 16.1659(6) Ågamma = 90 deg. Volume 5002.7(3) Å³ Z, Calculated density 4, 1.277 Mg/m³Absorption coefficient 0.094 mm⁻¹ F(000) 2032 Crystal size 0.75 × 0.32 ×0.30 mm Theta range for data collection 2.58 to 26.12 deg. Limitingindices −47 <= h <= 47, −9 <= k <= 9, −19 <= l <= 19 Reflectionscollected/unique 51621/9796 [R(int) = 0.0350] Completeness to theta =26.12 98.8% Absorption correction Multi-scan (Blessing, 1995) Max. andmin. transmission 0.745 and 0.645 Refinement method Full-matrixleast-squares on F² Data/restraints/parameters 9796/43/662Goodness-of-fit on F² 1.079 Final R indices [I > 2sigma(I)] R1 = 0.0484,wR2 = 0.1253 R indices (all data) R1 = 0.0525, wR2 = 0.1285 Absolutestructure parameter 0.0(7) (indeterminate) Largest diff. peak and hole0.332 and −0.454 e.A⁻³

TABLE 4 Crystal Data for Compound 16 Empirical formula C59 H56 Cl N3 O16Formula weight 1098.52 Temperature 123(2) K Wavelength 1.54178 A Crystalsystem, space group Monoclinic, P21 Unit cell dimensions a = 14.8343(11)A alpha = 90 deg. b = 8.4771(6) A beta = 91.780(7) deg. c = 21.8112(17)A gamma = 90 deg. Volume 2741.5(4) A{circumflex over ( )}3 Z, Calculateddensity 2, 1.331 Mg/m{circumflex over ( )}3 Absorption coefficient 1.238mm{circumflex over ( )}−1 F(000) 1152 Crystal size 0.6 × 0.05 × 0.02 mmTheta range for data collection 6.62 to 43.49 deg. Limiting indices −13<= h <= 13, −7 <= k <= 7, −19 <= l <= 19 Reflections collected/unique19701/3962 [R(int) = 0.1013] Completeness to theta = 43.49 99.3%Absorption correction Semi-empirical from equivalents Refinement methodFull-matrix least-squares on F{circumflex over ( )}2Data/restraints/parameters 3962/55/666 Goodness-of-fit on F{circumflexover ( )}2 1.093 Final R indices [I > 2sigma(I)] R1 = 0.0880, wR2 =0.2135 R indices (all data) R1 = 0.1479, wR2 = 0.2800 Absolute structureparameter 0.01(8) Extinction coefficient 0.0110(13) Largest diff. peakand hole 0.289 and −0.247 e.A{circumflex over ( )}−3

TABLE 5 Crystal Data for Compound 27 Empirical formula C44 H46 Cl N3 O14Formula weight 876.29 Temperature 164(2) K Wavelength 1.54178 Å Crystalsystem, space group Orthorhombic, P2₁2₁2₁ Unit cell dimensions a =8.1104(2) Å alpha = 90 deg. b = 19.5548(6) Å beta = 90 deg. c =27.2321(19) Å gamma = 90 deg. Volume 4318.9(4) Å³ Z, Calculated density4, 1.348 Mg/m³ Absorption coefficient 1.389 mm⁻¹ F(000) 1840 Crystalsize 1.0 × 0.13 × 0.11 mm Theta range for data collection 6.65 to 58.93deg. Limiting indices −6 <= h <= 8, −21 <= k <= 21, −30 <= l <= 30Reflections collected/unique 34329/6132 [R(int) = 0.0454] Completenessto theta = 58.93 99.3% Absorption correction Semi-empirical fromequivalents Max. and min. transmission 1.0, 0.717 Refinement methodFull-matrix least-squares on F² Data/restraints/parameters 6132/10/527Goodness-of-fit on F² 1.105 Final R indices [I > 2sigma(I)] R1 = 0.0638,wR2 = 0.1785 R indices (all data) R1 = 0.0827, wR2 = 0.1975 Absolutestructure parameter 0.17(4) (Flack, 1983) Largest diff. peak and hole0.415 and −0.347 e.A⁻³

Example 4 Determination of BACE-1 Inhibition by In Vitro FRET PeptideCleavage Assay

The ability of compounds of the invention to inhibit BACE-1 cleavage ofAPP is assessed using a fluorescent resonance energy transfer (FRET)peptide cleavage assay employing the FRET peptide HiLyte488-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Lys(QXL520)-OH (Anaspec, Inc., CA,USA; Cat no. 60604-01). When intact, the amino terminal fluorophore isquenched, but upon enzymatic cleavage the fluorophore is released fromquencher and fluoresces (520 nm). Assays are performed in triplicate in96 well black plates (20 mM sodium acetate, 0.1% Triton-X-100, pH 4.5;2.2 ng peptide per well and 25 ng/well of recombinant human BACE-1 (R &D Systems Cat no. 931-AS). The appropriate controls for enzyme activity(substrate plus enzyme, and substrate only) are employed and plates areincubated (1 h, 25° C., with activity stopped with 2.5 M sodiumacetate). Compounds of the invention are added in the concentrationrange from 100-0.0001 μg/mL. Fluorescence 480ex/520em is measured on aPolarstar plate reader (BMG LabTechnologies, UK) and data are analysedby plotting log₁₀ concentration of compound against percent inhibitionand fitting a logistic dose response sigmoidal curve using OriginPro 8(OriginLabs, Mass, USA).

TABLE 6 Inhibition of BACE-1 by Compounds of the Invention Compound No.IC₅₀ μg/mL Heparin 0.002 (MW average 12 kDa) NAcLMWH 0.007 (MW average 4kDa) 87 0.56 86 1.9 91 0.012 90 0.010 89 0.66 88 0.53 92 0.011 101 0.26111 0.22 135 0.38 123 0.37 148 0.007 147 0.1 149 0.005

Example 5 Factor Xa Anticoagulant Assay Protocol

The compound of the invention, standard or control (5 μl), is pipettedin assay buffer (0.9% sodium chloride) into a 96 well plate (Costar3595) and 19 μl of 0.03 IU/ml human Antithrombin III (AmericanDiagnostica Inc., product No. 433) in assay buffer is added to eachwell. The plate is incubated for two minutes at 37° C. 19 μl of bovineFactor Xa (14 nkat/ml; Thermo Scientific; product No. 32521) in assaybuffer is added to each well and incubated for one minute at 37° C. 19μl of 2.5 mM chromogenic substrate (American Diagnostica Inc.Spectrozyme FXa Product No 222L) in assay buffer is added to each welland incubated for 2 hours at 37° C., followed by addition of 5 μl of 30%acetic acid to each well. Absorbance at 405 nm is read on a multiplatereader.

All compounds are tested in the dose range 0.004 to 50 μg/ml and nonedisplay any measurable ability to accelerate antithrombin-III mediatedinactivation of Factor Xa, as measured by cleavage of a peptidesubstrate.

Although the invention has been described by way of example, it shouldbe appreciated the variations or modifications may be made withoutdeparting from the scope of the invention. Furthermore, when knownequivalents exist to specific features, such equivalents areincorporated as if specifically referred to in the specification.

INDUSTRIAL APPLICABILITY

The invention relates to compounds that are inhibitors of BACE-1. Thecompounds are therefore indicated for the treatment or prevention ofdiseases in which the inhibition of BACE-1 is desirable, e.g.neurodegenerative disorders such as senile dementia, pre-seniledementia, multi-infarct dementia or Alzheimer's disease.

1. An octasaccharide, decasaccharide or dodecasaccharide compound of theformula (I):H-Q-V-W-X-Y-Z-A   (I) where: A is an optionally substituted alkoxy,aralkoxy, aryloxy group; W, X, Y and Z are each independently adisaccharide of formula (i); V is a disaccharide of formula (i) or V isabsent; and Q is a disaccharide of formula (i) or Q is absent

where: R¹ is SO₃H; R² is H; R³ is acyl; R⁴ is H or SO₃H; and each R⁵ andR⁶ is independently selected from COOH and H; provided that one of R⁵and R⁶ in each disaccharide is H and the other is COOH; and providedthat all R³ groups in the octasaccharide, decasaccharide ordodecasaccharide are the same as each other and provided that all R⁴groups in the octasaccharide, decasaccharide or dodecasaccharide are thesame as each other; or a pharmaceutically acceptable salt thereof.
 2. Acompound as claimed in claim 1 where R⁵ is H and R⁶ is COOH or a saltform of COOH.
 3. A compound as claimed in claim 1 where R⁵ is COOH or asalt form of COOH and R⁶ is H.
 4. A compound as claimed in claim 1 whichcontains at least one disaccharide of formula (i) where R⁵ is H and R⁶is COOH or a salt form of COOH and at least one disaccharide of formula(i) where R⁵ is COOH or a salt form of COOH and R⁶ is H.
 5. A compoundas claimed in any one of claims 1 to 4 where the pharmaceuticallyacceptable salt is an ammonium salt, a metal salt, a salt of an organiccation, or a mixture thereof.
 6. A compound as claimed in any one ofclaims 1 to 5 where Q and V are absent and the compound of formula (I)is an octasaccharide.
 7. A compound as claimed in any one of claims 1 to5 where one of Q and V is a disaccharide of formula (i) and the other isabsent and the compound of formula (I) is a decasaccharide.
 8. Acompound as claimed in any one of claims 1 to 5 where Q and V are eachindependently a disaccharide of formula (i) and the compound of formula(I) is a dodecasaccharide.
 9. A compound as claimed in any one of claims1 to 8 where R³ is an acetyl group.
 10. A compound as claimed in any oneof claims 1 to 9 where R⁴ is SO₃H or a salt form of SO₃H.
 11. A compoundas claimed in any one of claims 1 to 10 where R¹ is a salt form of SO₃H.12. A compound as claimed in any one of claims 1 to 11 where A is anoptionally substituted aryloxy group.
 13. A compound as claimed in claim1, selected from the group consisting of:


14. A compound as claimed in claim 1, selected from the group consistingof

or a pharmaceutically acceptable salt thereof.
 15. A crystallinecompound of formula 13, 14, 15, 16 or 27:


16. A pharmaceutical composition comprising a pharmaceutically effectiveamount of a compound as claimed in any one of claims 1 to 14 andoptionally a pharmaceutically acceptable carrier, diluent or excipient.17. A method of treating or preventing a disease or disorder in which itis desirable to inhibit BACE-1 comprising administering apharmaceutically effective amount of a compound as claimed in any one ofclaims 1 to 14 to a patient requiring treatment.
 18. A method as claimedin claim 17 where the disease or disorder is senile dementia, pre-seniledementia, multi-infarct dementia or Alzheimer's disease.